Chronic pulmonary hypertension‐the monocrotaline model and involvement of the hemostatic system

References

• Adams , R. and Rogers , E. F. 1939 . The structure of monocrotaline, the alkaloid in Crotalaria spectabilis and Crotalaria retusa. I . J. Am. Chem. Soc. , 61 : 2815 – 2819 .
   Google Scholar
• Allen , J. R. and Carstens , L. A. 1970 . Pulmonary vascular occlusions initiated by endothelial lysis in monocrotaline‐intoxicated rats . Exp. Mol. Pathol. , 13 : 159 – 171 .
   PubMed Web of Science ®Google Scholar
• Allen , J. R. and Carstens , L. A. 1971 . Monocrotaline‐induced Budd‐Chiari syndrome in monkeys . Am. J. Digest. Dis. , 16 : 111 – 121 .
   PubMedGoogle Scholar
• Allen , J. R. and Chesney , C. F. 1972 . Effect of age on development of cor pulmonale in non‐human primates following pyrrolizidine alkaloid intoxication . Exp. Mol. Pathol. , 17 : 220 – 232 .
   PubMedGoogle Scholar
• Allen , J. R. , Childs , G. R. and Cravens , W. W. 1960 . Crotalaria spectabilis toxicity in chickens . Proc. Soc. Exp. Biol. Med. , 104 : 434 – 436 .
   PubMed Web of Science ®Google Scholar
• Allen , J. R. , Lalich , J. J. and Schmittle , S. C. 1963 . Crotalaria spectabilis induced cirrhosis in turkeys . Lab. Invest. , 12 : 512 – 517 .
   PubMedGoogle Scholar
• Allen , J. R. , Carstens , L. A. and Knezevic , A. L. 1965 . Crotalaria spectabilis intoxication in rhesus monkeys . Am. J. Vet. Res. , 26 : 753 – 757 .
   PubMedGoogle Scholar
• Allen , J. R. , Chesney , C. F. and Frazee , W. J. 1972 . Modifications of pyrrolizidine alkaloid intoxication resulting from altered hepatic microsomal enzymes . Toxicol. Appl. Pharmacol. , 23 : 470 – 479 .
   PubMed Web of Science ®Google Scholar
• Altiere , R. J. , Olson , J. W. and Gillespie , M. N. 1986 . Altered pulmonary vascular smooth muscle responsiveness in monocrotaline‐induced pulmonary hypertension . J. Pharmacol. Exp. Ther. , 236 : 390 – 395 .
   PubMed Web of Science ®Google Scholar
• Arcot , S. S. , Lipke , D. W. , Gillespie , M. N. and Olson , J. W. 1993 . Alteration of growth factor transcripts in rat lungs during development of monocrotaline‐induced pulmonary hypertension . Biochem. Pharmacol. , 46 : 1086 – 1091 .
   PubMed Web of Science ®Google Scholar
• Arcot , S. S. , Fagerland , J. A. , Lipke , D. W. , Gillespie , M. N. and Olson , J. W. 1995 . Basic fibroblast growth factor alterations during development of monocrotaline‐induced pulmonary hypertension in rats . Growth Factors , 12 : 121 – 130 .
   PubMed Web of Science ®Google Scholar
• Assoian , R. K. and Sporn , M. B. 1986 . Type B transforming growth factor in human platelets: Release during platelet degranulation and action on vascular smooth muscle cells . J. Cell Biol. , 102 : 1217 – 1223 .
   PubMed Web of Science ®Google Scholar
• Astrup , T. and Albrechtsen , O. K. 1957 . Estimation of the plasminogen activator and the trypsin inhibitor in animal and human tissues . Scand. J. Clin. Lab. Invest. , 9 : 233 – 243 .
   PubMed Web of Science ®Google Scholar
• Atarashi , K. , Mulrow , P. J. and Franco‐Saenz , R. 1984 . Inhibition of aldosterone production by atrial extract . Science , 224 : 992 – 994 .
   PubMed Web of Science ®Google Scholar
• Bachman , F. and Kruithof , E. K. O. 1984 . Tissue plasminogen activator: Chemical and physiological aspects . Semin. Thromb. Hemostasis. , 10 : 6 – 17 .
   PubMedGoogle Scholar
• Becker , R. B. , Neal , W. M. , Arnold , P. T. D. and Shealy , A. L. 1935 . A study of the payability and possible toxicity of 11 species of Crotalaria especially of C. spectabilis . J. Agric. Res. , 50 : 911 – 922 .
   Google Scholar
• Benditt , E. P. and Schwartz , S. M. 1988 . “ Blood vessels ” . In Pathology , Edited by: Rubin , E. and Farber , J. L. 452 – 541 . Philadelphia : J. B. Lipincott .
   Google Scholar
• Benveniste , J. and Chignard , M. 1985 . A role for PAF‐acether (platelet‐activating factor) in platelet‐dependent vascular diseases . Circulation , 72 : 713 – 717 .
   PubMed Web of Science ®Google Scholar
• Benveniste , J. , Hensen , P. M. and Cochrane , C. G. 1972 . Leukocyte‐dependent histamine release from rabbit platelets: The role of IgE, basophils, and a platelet‐activating factor . J. Exp. Med. , 136 : 1356 – 1377 .
   PubMed Web of Science ®Google Scholar
• Berk , B. C. , Alexander , R. W. , Brock , T. A. , Gimbrone , M. A. and Webb , R. C. 1986 . Vasoconstriction: A new activity for platelet‐derived growth factor . Science , 232 : 87 – 90 .
   PubMed Web of Science ®Google Scholar
• Bevilacqua , M. P. , Pober , J. S. , Majeau , G. R. , Cotran , R. S. and Gimbrone , M. A. 1984 . Interleukin (IL‐1) induces biosynthesis and cell surface expression of procoagulant activity in human vascular endothelial cells . J. Exp. Med. , 160 : 618 – 623 .
   PubMed Web of Science ®Google Scholar
• Bevilacqua , M. P. , Schleef , R. R. , Gimbrone , M. A. and Loskutoff , D. J. 1986 . Regulation of the fibrinolytic system of cultured human vascular endothelium by interleukin 1 . J. Clin. Invest. , 78 : 587 – 591 .
   PubMed Web of Science ®Google Scholar
• Bick , R. L. and Kunkel , L. 1992 . Hypercoagulability and thrombosis . Lab. Med. , 23 : 233 – 238 .
   Google Scholar
• Bjornsson , J. and Edwards , W. D. 1985 . Primary pulmonary hypertension: a histologie study of 80 cases . Mayo Clin. Proc. , 60 : 16 – 25 .
   PubMed Web of Science ®Google Scholar
• Bloom , A. L. 1990 . Physiology of blood coagulation . Haemostasis , 20 (suppl. 1) : 14 – 29 .
   PubMedGoogle Scholar
• Bonner , H. 1988 . “ The blood and lymphoid organs ” . In Pathology , Edited by: Rubin , E. and Farber , J. L. 1014 – 1117 . Philadelphia : J. B. Lipincott .
   Google Scholar
• Bruner , L. H. , Hilliker , K. S. and Roth , R. A. 1983 . Pulmonary hypertension and ECG changes from monocrotaline pyrrole in the rat . Am. J. Physiol. , 245 : H300 – H306 . (Heart Circ. Physiol. 14)
   PubMed Web of Science ®Google Scholar
• Bruner , L. H. , Carpenter , L. J. , Hamlow , P. and Roth , R. A. 1986 . Effect of a mixed function oxidase inducer and inhibitor on monocrotaline pyrrole pneumotoxicity . Toxicol. Appl. Pharmacol. , 85 : 416 – 127 .
   PubMed Web of Science ®Google Scholar
• Bull , L. B. , Culvenor , C. C. J. and Dick , A. T. 1968 . The pyrrolizidine alkaloids. Their chemistry‐pathogenicity and other properties , Edited by: Neuberger , A. and Tatum , E. L. 1 – 32 . 40 – 68 . 167 215 – 219 . 234 – 262 . Amsterdam : North‐Holland .
   Google Scholar
• Bummer , P. M. , Baughn , J. A. , Sanders , L. P. , Absher , K. R. , O'Connor , W.N. , Olson , J. W. and Gillespie , M. N. 1994 . Surfactant disposition in rats with monocrotaline‐induced pneumotoxicity . Toxicology , 90 : 53 – 62 .
   PubMedGoogle Scholar
• Burch , G. H. , Jensen , L. R. , Pappas , J. , Hammond , E. H. , Banner , W. Jr. and Shaddy , R. E. 1996 . Growth factor expression and effects of amrinone in monocrotaline‐induced pulmonary hypertension in rats . Biochem. Mol. Med. , 58 : 204 – 210 .
   PubMedGoogle Scholar
• Busch , C. and Owen , W. G. 1982 . Identification in vitro of an endothelial cell surface cofactor for antithrombin III. Parallel studies with isolated perfused rat hearts and microcarrier cultures of bovine endothelium . J. Clin. Invest. , 69 : 726 – 729 .
   PubMedGoogle Scholar
• Butler , W. H. 1970 . An ultrastructural study of the pulmonary lesion induced by pyrrole derivatives of the pyrrolizidine alkaloids . J. Pathol. , 102 : 15 – 19 .
   PubMed Web of Science ®Google Scholar
• Butler , W. H. , Mattocks , A. R. and Barnes , J. M. 1970 . Lesions in the liver and lungs of rats given pyrrole derivatives of pyrrolizidine alkaloids . J. Pathol. , 100 : 169 – 175 .
   PubMed Web of Science ®Google Scholar
• Carpenter , G. and Cohen , S. 1979 . Epidermal growth factor . Annu. Rev. Biochem. , 48 : 193 – 216 .
   PubMed Web of Science ®Google Scholar
• Cassis , L. A. , Rippetoe , P. E. , Soltis , E. E. , Painter , D. J. , Fitz , R. and Gillespie , M. N. 1992 . Angiotensin II and monocrotaline‐induced pulmonary hypertension: Effect of losartan (DuP 753), a nonpeptide angiotensin type 1 receptor antagonist . J. Pharmacol. Exp. Ther. , 262 : 1168 – 1172 .
   PubMed Web of Science ®Google Scholar
• Cassis , L. , Shenoy , U. , Lipke , D. , Baughn , J. , Fettinger , M. and Gillespie , M. 1997 . Lung angiotensin receptor binding characteristics during the development of monocrotaline‐induced pulmonary hypertension . Biochem. Pharmacol. , 54 : 27 – 31 .
   PubMedGoogle Scholar
• Cerveny , T. J. , Fass , D. M. and Mann , K. G. 1984 . Synthesis of coagulation factor V by cultured aortic endothelium . Blood , 63 : 1467 – 1474 .
   PubMed Web of Science ®Google Scholar
• Chao , J. , Simson , J. A. , Chung , P. , Chen , L. M. and Chao , L. 1993 . Regulation of kininogen gene expression and localization in the lung after monocrotaline‐induced pulmonary hypertension in rats . Proc. Soc. Exp. Biol. Med. , 203 : 243 – 250 .
   PubMed Web of Science ®Google Scholar
• Cheeke , P. R. 1989 . “ Pyrrolizidine alkaloid toxicity and metabolism in laboratory animals and livestock ” . In Toxicants of plant origin, Vol. I, Alkaloids , Edited by: Cheeke , P. R. Vol. I , 2 – 22 . Boca Raton, FL : CRC Press .
   Google Scholar
• Cheeke , P. R. and Pierson‐Goeger , M. L. 1983 . Toxicity of Senecio jacobaea and pyrrolizidine alkaloids in various laboratory animals and avian species . Toxicol. Lett. , 18 : 343 – 349 .
   PubMed Web of Science ®Google Scholar
• Chen , E. P. , Bittner , H. B. , Davis , R. D. and Van Trigt , P. 1997 . Right ventricular failure—Insights provided by a new model of chronic pulmonary hypertension . Transplantation , 63 : 209 – 216 .
   PubMedGoogle Scholar
• Chesney , C. F. and Allen , J. R. 1973a . Resistance of the guinea pig to pyrrolizidine alkaloid intoxication . Toxicol. Appl. Pharmacol. , 26 : 385 – 392 .
   PubMedGoogle Scholar
• Chesney , C. F. and Allen , J. R. 1973b . Endocardial fibrosis associated with monocrotaline‐induced pulmonary hypertension in nonhuman primates (Macaca arctoides) . Am. J. Vet. Res. , 34 : 1577 – 1581 .
   PubMed Web of Science ®Google Scholar
• Chesney , C. F. , Allen , J. R. and Hsu , I. C. 1974a . Right ventricular hypertrophy in monocrotaline pyrrole treated rats . Exp. Mol. Pathol. , 20 : 257 – 268 .
   PubMed Web of Science ®Google Scholar
• Chesney , C. F. , Hsu , I. C. and Allen , J. R. 1974b . Modifications of the in vitro metabolism of the hepatotoxic pyrrolizidine alkaloid, monocrotaline . Res. Commun. Chem. Pathol. Pharmacol. , 8 : 567 – 570 .
   PubMedGoogle Scholar
• Coflesky , J. T. , Adler , K. B. , Woodcook‐Mitchell , J. , Mitchell , J. and Evans , J. N. 1988 . Proliferative changes in the pulmonary arterial wall during short‐term hyperoxic injury to the lung . Am. J. Pathol. , 132 : 563 – 573 .
   PubMedGoogle Scholar
• Collen , D. 1980 . On the regulation and control of fibrinolysis . Thromb. Hemostasis. , 43 : 77 – 89 .
   PubMed Web of Science ®Google Scholar
• Colman , R. W. , Hirsh , J. , Marder , V. J. and Salzman , E. W. , eds. 1987 . Hemostasis and thrombosis, , 2nd ed. , Philadelphia : J. B. Lippincott .
   Google Scholar
• Colucci , M. , Paramo , J. A. and Collen , D. 1985 . Generation in plasma of a fast‐acting inhibitor of plasminogen activator in response to endotoxin stimulation . J. Clin. Invest. , 75 : 818 – 824 .
   PubMed Web of Science ®Google Scholar
• Conney , A. H. 1967 . Pharmacological implications of microsomal enzyme induction . Pharmacol. Rev. , 19 : 317 – 354 .
   PubMed Web of Science ®Google Scholar
• Connors , A. F. , McCaffree , D. R. and Rogers , R. M. 1981 . The adult respiratory distress syndrome . Dis. Monogr. , 27 : 1 – 75 .
   PubMedGoogle Scholar
• Cooper , D. R. , Lewis , G. P. , Lieberman , G. E. , Webb , H. and Westwick , J. 1979 . ADP metabolism in vascular tissue, a possible thromboregulatory mechanism . Thromb. Res. , 14 : 901 – 914 .
   PubMed Web of Science ®Google Scholar
• Crutchley , D. J. 1987 . “ Hemostatic potential of the pulmonary endothelium ” . In Lung biology in health and disease. Pulmonary endothelium in health and disease , Edited by: Ryan , U. S. vol. 32 , 237 – 273 . New York : Marcel Dekker .
   Google Scholar
• Crutchley , D. J. , Eling , T. E. and Anderson , M. W. 1978 . ADPase activity of isolated perfused rat lung . Life Sci. , 22 : 1413 – 1420 .
   PubMedGoogle Scholar
• Crutchley , P. J. , Ryan , J. W. , Ryan , U. S. and Fisher , G. H. 1983 . Bradykinin‐induced release of prostacyclin and thromboxanes from bovine pulmonary endothelial cells. Studies with lower homologs and calcium antagonists . Biochim. Biophys. Acta , 751 : 99 – 107 .
   PubMedGoogle Scholar
• Crutchley , D. J. , Ryan , U. S. and Ryan , J. W. 1985 . Glucocorticoid modulation of prostacyclin production in cultured bovine pulmonary endothelial cells . J. Pharmacol. Exp. Ther. , 233 : 650 – 655 .
   PubMedGoogle Scholar
• Culvenor , C. C. J. and Dal Bon , R. 1964 . Carbonyl stretching frequencies of pyrrolizidine alkaloids . Aust. J. Chem. , 17 : 1296 – 1300 .
   Google Scholar
• Curriden , S. A. , Podor , T. J. and Loskutoff , D. J. 1988 . “ The fibrinolytic system of cultured endothelial cells ” . In Endothelial cell biology in health and disease , Edited by: Simionescu , N. and Simionescu , M. 229 – 252 . New York : Plenum Press .
   Google Scholar
• Currie , M. G. , Geller , D. M. and Cole , B. R. 1983 . Bioactive cardiac substances: Potent vasorelaxant activity in mammalian atria . Science , 221 : 71 – 73 .
   PubMed Web of Science ®Google Scholar
• Davies , P. , Jones , R. C. , Schloo , B. L. and Reid , L. M. 1987 . “ Endothelium of the pulmonary vasculature in health and disease ” . In Lung biology in health and disease. Pulmonary endothelium in health and disease , Edited by: Ryan , U. S. vol. 32 , 375 – 445 . New York : Marcel Dekker .
   Google Scholar
• DeBold , A. J. , Borenstein , H. B. , Veress , A. T. and Sonnenberg , H. 1981 . A rapid and potent natriuretic response to intravenous injection of atrial myocardial extract in rats . Life Sci. , 28 : 89 – 94 .
   PubMed Web of Science ®Google Scholar
• Dichek , D. and Quertermous , T. 1989 . Thrombin regulation of mRNA levels of tissue plasminogen activator and plasminogen activator inhibitor‐1 in cultured human umbilical vein endothelial cells . Blood , 74 : 222 – 228 .
   PubMed Web of Science ®Google Scholar
• Dickinson , J. O. 1980 . Release of pyrrolizidine alkaloids into milk . Proc. West. Pharmacol. Soc. , 23 : 377 – 379 .
   PubMedGoogle Scholar
• Dzau , V. J. , Gibbons , G. H. and Pratt , E. R. 1991 . Molecular mechanisms of vascular rennin‐angiotensin system in myointimal hyperplasia . Hypertension , 18 (suppl II) : 100 – 105 .
   Google Scholar
• Edelberg , J. M. , Sane , D. C. and Pizzo , S. V. 1994 . Vascular regulation of plasminogen activator inhibitor‐1 activity . Semin. Thromb. Hemostasis , 20 : 319 – 323 .
   PubMed Web of Science ®Google Scholar
• Eisenberg , P. R. , Lucore , C. , Kaufman , L. , Sobel , B. E. , Jaffe , A. S. and Rich , S. 1990 . Fibrinopeptide A levels indicative of pulmonary vascular thrombosis in patients with primary pulmonary hypertension . Circulation , 82 : 841 – 847 .
   PubMed Web of Science ®Google Scholar
• Emmel , M. W. , Sanders , D. A. and Healey , W. W. 1935 . Crotalaria spectabilis Roth seed poisoning in swine . J. Am. Vet. Med. Assoc. , 86 : 43 – 54 .
   Google Scholar
• Erickson , L. A. , Schleef , R. R. , Ny , T. and Loskutoff , D. J. 1985 . “ The fibrinolytic system of the vascular wall ” . In Clinics in haematology , Edited by: Ruggeri , Z. M. vol. 14 , 513 – 529 . Philadelphia : Saunders . (2),
   Google Scholar
• Esmon , C. T. 1987 . The regulation of natural anticoagulant pathways . Science , 235 : 1348 – 1352 .
   PubMed Web of Science ®Google Scholar
• Esmon , C. T. 1988 . “ Assembly and function of the protein C anticoagulant pathway on endothelium ” . In Endothelial cell biology in health and disease , Edited by: Simionescu , N. and Simionescu , M. 191 – 206 . New York : Plenum Press .
   Google Scholar
• Esmon , C. T. , Esmon , N. L. and Harris , K. W. 1982a . Complex formation between thrombin and thrombomodulin inhibits both thrombin‐catalyzed fibrin formation and factor V activation . J. Biol. Chem. , 257 : 7944 – 7947 .
   PubMed Web of Science ®Google Scholar
• Esmon , N. L. , Owen , W. G. and Esmon , C. T. 1982b . Isolation of a membrane‐bound cofactor for thrombin‐catalyzed activation of protein C . J. Biol. Chem. , 257 : 859 – 864 .
   PubMed Web of Science ®Google Scholar
• Estep , J. E. , Lame , M. W. , Jones , D. A. and Segall , H. J. 1990 . N‐Acetylcysteine‐conjugated pyrrole identified in rat urine following administration of two pyrrolizidine alkaloids, monocrotaline and senecionine . Toxicol. Lett. , 54 : 61 – 69 .
   PubMed Web of Science ®Google Scholar
• Estep , J. E. , Lame , M. W. , Morin , D. , Jones , A. D. , Wilson , D. W. and Segall , H. J. 1991 . [14C]Monocrotaline kinetics and metabolism in the rat . Drug Metab. Dispos. , 19 : 135 – 139 .
   PubMed Web of Science ®Google Scholar
• Falk , D. K. 1984 . Pulmonary disease in idiopathic urticarial vasculitis . Am. Acad. Dermatol. , 11 : 346 – 352 .
   PubMedGoogle Scholar
• Fasules , J. W. , Stenmark , K. R. , Hensen , P. M. , Voelkel , N. F. and Reeves , J. T. 1987 . Neither anticoagulant nor nonanticoagulant heparin affects monocrotaline lung injury . J. Appl. Physiol. , 62 : 816 – 820 .
   PubMedGoogle Scholar
• Fernandez‐Segoviano , P. , Estaban , A. and Martinez‐Cubruja , R. 1983 . Pulmonary vascular lesions in the toxic oil syndrome in Spain . Thorax , 38 : 724 – 729 .
   PubMed Web of Science ®Google Scholar
• Findlay , S. R. , Lichtenstein , L. M. , Hanahan , D. J. and Pickard , R. N. 1981 . Contraction of guinea pig ileal smooth muscle by actetly glyceryl ether phosphorylcholine . Am. J. Physiol. , 241 : C130 – C133 .
   Google Scholar
• Fishman , A. P. 1997 . Appetite‐suppressant drugs and primary pulmonary hypertension [letter] . N. Engl. J. Med. , 336 : 511
   PubMedGoogle Scholar
• Fullerton , D. A. , Hahn , A. R. and McIntyre , R. C. Jr. 1996 . Mechanistic imbalance of pulmonary vasomotor control in progressive lung injury . Surgery , 119 : 98 – 103 .
   PubMedGoogle Scholar
• Fuster , V. , Steele , P. M. , Edwards , W. D. , Gersh , B. J. , McGoon , M. D. and Frye , R. L. 1984 . Primary pulmonary hypertension: natural history and the importance of thrombosis . Circulation , 70 : 580 – 587 .
   PubMed Web of Science ®Google Scholar
• Ganey , P. E. and Roth , R. A. 1986 . Thromboxane does not mediate pulmonary vascular response to monocrotaline pyrrole . Am. J. Physiol. , 252 : H743 – H748 . (Heart Circ. Physiol. 21)
   Google Scholar
• Ganey , P. E. and Roth , R. A. 1987a . 6‐Ketoprostaglandin F1α and thromboxane B2 in isolated, buffer‐perfused lungs from monocrotaline pyrrole‐treated rats . Exp. Lung Res. , 12 : 195 – 206 .
   PubMed Web of Science ®Google Scholar
• Ganey , P. E. and Roth , R. A. 1987b . 5‐hydroxytryptamine and thromboxane in platelets from rats treated with monocrotaline pyrrole . Toxicol. Appl. Pharmacol. , 88 : 157 – 164 .
   PubMedGoogle Scholar
• Ganey , P. E. and Roth , R. A. 1988 . 6‐Ketoprostaglandin F1α and thromboxane B2 in isolated, blood‐perfused lungs from monocrotaline‐treated rats . J. Toxicol. Environ. Health , 23 : 127 – 137 .
   PubMed Web of Science ®Google Scholar
• Ganey , P. E. , Fink , G. D. and Roth , R. A. 1985 . The effect of dietary restriction and altered sodium intake on the cardiopulmonary toxicity of monocrotaline pyrrole . Toxicol. Appl. Pharmacol. , 78 : 55 – 62 .
   PubMed Web of Science ®Google Scholar
• Ganey , P. E. , Sprugel , K. H. , Hadley , K. B. and Roth , R. A. 1986 . Monocrotaline pyrrole‐induced cardiopulmonary toxicity is not altered by metergoline or ketanserin . J. Pharmacol. Exp. Ther. , 237 : 226 – 231 .
   PubMedGoogle Scholar
• Ganey , P. E. , Sprugel , K. H. , White , S. M. , Wagner , J. G. and Roth , R. A. 1988 . Pulmonary hypertension due to monocrotaline pyrrole is reduced by moderate thrombocytopenia . Am. J. Physiol. , 255 : H1165 – H1172 . (Heart Circ. Physiol. 24)
   Google Scholar
• Gardiner , M. R. , Royce , R. and Bokor , A. 1965 . Studies on Crotalaria crispata, a newly recognized cause of Kimberley horse disease . J. Pathol. Bacteriol. , 89 : 43 – 55 .
   PubMedGoogle Scholar
• Ge , M. , Ryan , T. J. and Malik , A. B. 1991 . “ Pulmonary endothelium and coagulation ” . In The lung , Edited by: Crystal , R. G. and West , J. B. vol. 1 , 329 – 336 . New York : Raven Press .
   Google Scholar
• Geggel , R. L. , Hu , L. M. and Reid , L. M. 1986 . Effect of heparin during chronic hypoxia: a hemodynamic study including acute hypoxia (abstr.) . Fed. Proc. , 45 : 943
   Google Scholar
• Geggel , R. L. , Carvalho , A. C. A. , Hover , L. W. and Reid , L. M. 1987 . Von Willebrand factor abnormalities in primary pulmonary hypertension . Am. Rev. Respir. Dis. , 135 : 294 – 299 .
   PubMedGoogle Scholar
• Gerard , R. D. and Meidell , R. S. 1989 . Regulation of tissue plasminogen activator expression . Annu. Rev. Physiol. , 51 : 245 – 262 .
   PubMedGoogle Scholar
• Gertler , J. P. and Abbott , W. M. 1992 . Prothrombotic and fibrinolytic function of normal and perturbed endothelium . J. Surg. Res. , 52 : 89 – 95 .
   PubMedGoogle Scholar
• Ghodsi , F. and Will , J. A. 1981 . Changes in pulmonary structure and function induced by monocrotaline intoxication . Am. J. Physiol. , 240 : H149 – H155 . (Heart Circ. Physiol. 9)
   PubMed Web of Science ®Google Scholar
• Gibbons , W. J. , Durr , H. E. and Cox , S. A. 1953 . An outbreak of cirrhosis of the liver in horses . North Am. Vet. , 34 : 556 – 558 .
   Google Scholar
• Giddings , J. C. 1986 . “ Von Willebrand factor‐Physiology ” . In Vascular endothelium in hemostasis and thrombosis , Edited by: Gimbrone , M. A. 142 – 168 . New York : Churchill Livingstone .
   Google Scholar
• Gillespie , M. N. , Frederick , W. B. , Altiere , R. J. , Olson , J. W. and Kimmel , E. C. 1985 . Pulmonary mechanical, ventilatory, and gas exchange abnormalities in rats with monocrotaline‐induced pulmonary hypertension . Exp. Lung Res. , 8 : 189 – 197 .
   Google Scholar
• Gillespie , M. N. , Olson , J. W. , Reinsel , C. N. , O'Connor , W.N. and Altiere , R. J. 1986 . Vascular hyperresponiveness in perfused lungs from monocrotaline‐treated rats . Am. J. Physiol. , 251 : H109 – H114 . (Heart Circ. Physiol. 20)
   Google Scholar
• Gillespie , M. N. , Rippetoe , P. E. , Haven , C. A. , Shiao , R. T. , Orlinska , U. , Maley , B. E. and Olson , J. W. 1989 . Polyamines and epidermal growth factor in monocrotaline‐induced pulmonary hypertension . Am. Rev. Respir. Dis. , 140 : 1462 – 1466 .
   Google Scholar
• Gillis , C. N. , Huxtable , R. J. and Roth , R. A. 1978 . Effects of monocrotaline pretreatment of rats on removal of S‐hydroxytryptamine and noradrenaline by perfused lung . Br. J. Pharmacol. , 63 : 435 – 443 .
   PubMed Web of Science ®Google Scholar
• Gimbrone , M. A. and Bevilacqua , M. P. 1988 . “ Vascular endothelium functional modulation at the blood interface ” . In Endothelial cell biology in health and disease , Edited by: Simionescu , N. and Simionescu , M. 255 – 273 . New York : Plenum Press .
   Google Scholar
• Glowaz , S. L. , Michnika , M. and Huxtable , R. J. 1992 . Detection of a reactive pyrrole in the hepatic metabolism of the pyrrolizidine alkaloid, monocrotaline . Toxicol. Appl. Pharmacol. , 115 : 168 – 173 .
   PubMed Web of Science ®Google Scholar
• Goldenthal , E. I. , D'Aguanno , W. and Lynch , J. F. 1964 . Hormonal modification of the sex differences following monocrotaline administration . Toxicol. Appl. Pharmacol. , 6 : 434 – 441 .
   PubMedGoogle Scholar
• Gorman , R. R. , Bunting , S. and Miller , O. V. 1977 . Modulation of human platelet adenylate cyclase by prostaglandin (PGX) . Prostaglandins , 13 : 377 – 388 .
   PubMed Web of Science ®Google Scholar
• Gospodarowicz , D. , Hirabayashi , L. , Giguere , L. and Tauber , J. P. 1981 . Factors controlling the pro‐liferative rate, final cell density, and life span of bovine vascular smooth muscle cells in culture . J. Cell. Biol. , 89 : 568 – 578 .
   PubMed Web of Science ®Google Scholar
• Gross , N. 1977 . Pulmonary effects of radiation therapy . Ann. Intern. Med. , 86 : 81 – 92 .
   PubMed Web of Science ®Google Scholar
• Gross , S. S. and Wolin , M. S. 1995 . Nitric oxide: Pathophysiologic mechanisms . Annu. Rev. Physiol. , 57 : 737 – 769 .
   PubMed Web of Science ®Google Scholar
• Habenicht , A. J. R. , Salbach , P. , Blattner , C. and Janssen‐Timmen , U. 1990 . “ Platelet‐derived growth factor: Formation and biological activities ” . In Growth factors, differentiation factors, and cytokines , Edited by: Habenicht , A. 31 – 41 . Berlin : Springer‐Verlag .
   Google Scholar
• Hacker , A. , Madden , J. and Choy , J. 1995 . Inhibition of nitric oxide production protects against monocrotaline‐induced pulmonary hypertension (abstr.) . Am. J. Respir. Crit. Care Med. , 151 : A730
   Google Scholar
• Hales , C. A. , Kradin , R. L. , Brandstetter , R. D. and Zhu , Y. 1983 . Impairment of hypoxic pulmonary artery remodeling by heparin in mice . Am. Rev. Respir. Dis. , 128 : 747 – 751 .
   PubMedGoogle Scholar
• Hamilton , K. K. and Sims , P. J. 1987 . Changes in cytosolic Ca2+ associated with von Willebrand factor release in human endothelial cells exposed to histamine: study of microcarrier cell monolayers using the fluorescent probe indo‐1 . J. Clin. Invest. , 79 : 600 – 608 .
   PubMed Web of Science ®Google Scholar
• Hampl , V. , Tristani‐Firouzi , M. , Hutsell , T. C. and Archer , S. L. 1996 . Nebulized nitric oxide/nucleophile adduct reduces chronic pulmonary hypertension . Cardiovasc. Res. , 31 : 55 – 62 .
   PubMed Web of Science ®Google Scholar
• Harpel , P. C. 1987 . “ Blood proteolytic enzyme inhibitors: their role in modulating blood coagulation and fibrinolytic enzyme pathways ” . In Hemostasis and thrombosis , Edited by: Colman , R. W. , Marder , V. J. , Salzman , E. W. and Hirsh , J. 219 – 234 . Philadelphia : J. B. Lippincott .
   Google Scholar
• Harris , P. N. , Anderson , R. C. and Chen , K. K. 1942 . The action of monocrotaline and retronecine . J. Pharmacol. Exp. Ther. , 75 : 78 – 82 .
   Google Scholar
• Hartmann , T. and Witte , L. 1995 . “ Chemistry, biology and chemoecology of the pyrrolizidine alkaloids ” . In Alkaloids: Chemical and biological perspectives , Edited by: Pelletier , S. W. vol. 9 , 156 – 233 . Oxford : Pergamon Press .
   Google Scholar
• Hassoun , P. , Kradin , R. , Thompson , T. and Hales , C. 1986 . Effect of heparin on hypoxic pulmonary hypertension and vascular remodeling (abstr.) . Am. Rev. Respir. Dis. , 133 : A228
   Google Scholar
• Hayashi , Y. 1966 . Excretion and alteration of monocrotaline in rats after a subcutaneous injection . Fed. Proc. , 25 : 688
   Google Scholar
• Hayashi , Y. and Lalich , J. J. 1967 . Renal and pulmonary alterations induced in rats by a single injection of monocrotaline . Proc. Soc. Exp. Biol. Med. , 124 : 392 – 396 .
   PubMed Web of Science ®Google Scholar
• Hayashi , Y. , Kato , M. and Otsuka , H. 1979 . Inhibitory effects of diet‐reduction on monocrotaline intoxication in rats . Toxicol. Lett. , 3 : 151 – 155 .
   Google Scholar
• Hayashi , Y. , Kokubo , T. , Takahashi , M. , Furukawa , F. , Otsuka , H. and Hashimoto , K. 1984 . Correlative morphological and biochemical studies on monocrotaline‐induced pulmonary alterations in rats . Toxicol. Lett. , 21 : 65 – 71 .
   PubMedGoogle Scholar
• Heath , D. 1969 . “ Pulmonary hypertension due to Crotalaria spectabilis. ” . In The pulmonary circulation and interstitial space , Edited by: Fishman , A. P. and Hecht , H. H. 305 – 319 . Chicago : University of Chicago Press .
   Google Scholar
• Heath , D. 1992 . The rat is a poor animal model for the study of human pulmonary hypertension . Cardioscience , 3 : 1 – 6 .
   PubMedGoogle Scholar
• Heath , D. and Smith , P. 1978 . The electron microscopy of “fibrinoid necrosis” in pulmonary arteries . Thorax , 33 : 579 – 595 .
   PubMedGoogle Scholar
• Heffner , J. E. , Shoemaker , S. A. , Canham , E. M. , Patel , M. , McMurtry , I. , Morris , H. G. and Repine , J. E. 1983 . Platelet‐induced pulmonary hypertension and edema . Chest , 5 (suppl.) : 78 – 79 .
   Google Scholar
• Heffner , J. E. , Sahn , S. A. and Repine , J. E. 1987 . The role of platelets in the adult respiratory distress syndrome . Am. Rev. Respir. Dis. , 135 : 482 – 492 .
   PubMed Web of Science ®Google Scholar
• Henderson , R. F. , Damon , E. G. and Henderson , T. R. 1978a . Early damage indicators in the lung. I. Lactate dehydrogenase activity in the airways . Toxicol. Appl. Pharmacol. , 44 : 291 – 297 .
   PubMed Web of Science ®Google Scholar
• Henderson , R. F. , Muggenburg , B. A. , Mauderly , J. L. and Tuttle , W. A. 1978b . Early damage indicators in the lung. II. Time sequence of protein accumulation and lipid loss in the airways of beagle dogs with beta irradiation of the lung . Radiat. Res. , 76 : 145 – 158 .
   PubMedGoogle Scholar
• Henderson , R. F. , Bensen , J. M. , Hahn , F. F. , Hobbs , C. H. , Jones , R. K. , Mauderly , J. L. , McClellan , R. O. and Pickrell , J. A. 1985 . New approaches for the evaluation of pulmonary toxicity: Bronchoalveolar lavage fluid analysis . Fundam. Appl. Toxicol. , 5 : 451 – 458 .
   PubMedGoogle Scholar
• Herget , J. , Palacek , F. , Preclik , P. , Cermakova , M. , Vizek , M. and Petrovicka , M. 1981 . Pulmonary hypertension induced by repeated inflammation in the rat . J. Appl. Physiol. , 51 : 755 – 761 .
   PubMedGoogle Scholar
• Hill , N. S. , O'Brien , R.F. and Rounds , S. 1984 . Repeated lung injury due to alpha‐naphthylurea causes right ventricular hypertrophy in rats . J. Appl. Physiol. , 56 : 388 – 396 .
   PubMedGoogle Scholar
• Hilliker , K. S. and Roth , R. A. 1984 . Alteration of monocrotaline pyrrole‐induced cardiopulmonary effects in rats by hydralazine, dexamethasone or sulfinpyrazone . Br. J. Pharmacol. , 82 : 375 – 380 .
   PubMedGoogle Scholar
• Hilliker , K. S. and Roth , R. A. 1985 . Increased vascular responsiveness in lungs of rats with pulmonary hypertension induced by monocrotaline pyrrole . Am. Rev. Respir. Dis. , 131 : 46 – 50 .
   PubMedGoogle Scholar
• Hilliker , K. S. , Bell , T. G. and Roth , R. A. 1982 . Pneumotoxicity and thrombocytopenia after a single injection of monocrotaline . Am. J. Physiol. , 242 : H573 – H579 . (Heart Circ. Physiol. 11)
   PubMed Web of Science ®Google Scholar
• Hilliker , K. S. , Garcia , C. M. and Roth , R. A. 1983a . Effects of monocrotaline pyrrole on 5‐hydroxy‐tryptamine and paraquat uptake by lung slices . Res. Commun. Chem. Pathol. Pharmacol. , 40 : 179 – 197 .
   PubMedGoogle Scholar
• Hilliker , K. S. , Bell , T. G. and Roth , R. A. 1983b . Monocrotaline pyrrole‐induced pulmonary hypertension in fawn‐hooded rats with platelet storage pool deficiency: 5‐Hydroxytryptamine uptake by isolated, perfused lungs . Thromb. Hemostasis , 50 : 844 – 847 .
   PubMedGoogle Scholar
• Hilliker , K. S. , Deyo , J. A. , Bell , T. G. and Roth , R. A. 1983c . Aggregation of platelets from monocrotaline pyrrole‐treated rats . Thromb. Res. , 32 : 325 – 333 .
   PubMedGoogle Scholar
• Hilliker , K. S. , Imlay , M. and Roth , R. A. 1984a . Effect of monocrotaline treatment on norepineph‐rine removal by isolated, perfused rat lungs . Biochem. Pharmacol. , 33 : 2690 – 2692 .
   PubMedGoogle Scholar
• Hilliker , K. S. , Bell , T. G. , Lorimer , D. and Roth , R. A. 1984b . Effects of thrombocytopenia on monocrotaline pyrrole induced pulmonary hypertension . Am. J. Physiol. , 246 : H747 – H753 . (Heart Circ. Physiol. 15)
   Google Scholar
• Hislop , A. and Reid , L. 1974 . Arterial changes in Crotalaria spectabilis‐induced pulmonary hypertension in rats . Br. J. Exp. Pathol. , 55 : 153 – 163 .
   PubMed Web of Science ®Google Scholar
• Hoorn , C. M. and Roth , R. A. 1992 . Monocrotaline pyrrole alters DNA, RNA and protein synthesis in pulmonary artery endothelial cells . Am. J. Physiol. , 262 : L740 – L747 . (Lung Cell. Mol. Physiol. 6)
   Google Scholar
• Hoorn , C. M. and Roth , R. A. 1993 . Monocrotaline pyrrole‐induced changes in angiotensin‐converting enzyme activity of cultured pulmonary artery endothelial cells . Br. J. Pharmacol , 110 : 597 – 602 .
   PubMed Web of Science ®Google Scholar
• Hosoda , Y. 1994 . Pathology of pulmonary hypertension: a human and experimental study . Pathol. Int. , 44 : 241 – 267 .
   PubMedGoogle Scholar
• Hsu , I. C. , Chesney , C. F. and Allen , J. R. 1973 . Chronic effects of monocrotaline pyrrole on hepatic mitosis and DNA synthesis . Proc. Soc. Exp. Biol. Med. , 142 : 1133 – 1136 .
   PubMedGoogle Scholar
• Huang , E. M. and Detwiler , T. C. 1986 . “ Stimulus‐response coupling mechanisms ” . In Biochemistry of platelets , Edited by: Phillips , D. R. and Shuman , M. A. 1 – 68 . Orlando, FL : Academic Press .
   Google Scholar
• Hughes , J. , Gillis , C. N. and Bloom , F. E. 1969 . The uptake and disposition of d,l‐norepinephrine in perfused rat lung . J. Pharmacol. Exp. Ther. , 169 : 237 – 248 .
   PubMed Web of Science ®Google Scholar
• Hurley , J. V. and Jago , M. V. 1975 . Pulmonary oedema in rats given dehydromonocrotaline: A topographic and electron microscopic study . J. Pathol. , 117 : 23 – 32 .
   PubMed Web of Science ®Google Scholar
• Huxtable , R. J. 1979 . New aspects of the toxicology and pharmacology of pyrrolizidine alkaloids . Gen. Pharmacol. , 10 : 159 – 167 .
   PubMedGoogle Scholar
• Huxtable , R. J. 1989 . “ Human health implications of pyrrolizidine alkaloids and herbs containing them ” . In Toxicants of plant origin, vol. I, Alkaloids , Edited by: Cheeke , P. R. vol. I , 41 – 86 . Boca Raton, FL : CRC Press .
   Google Scholar
• Huxtable , R. J. 1990 . Activation and pulmonary toxicity of pyrrolizidine alkaloids (T. E. Gram, special ed.) . Pharmacol. Ther. , 47 : 371 – 389 .
   PubMed Web of Science ®Google Scholar
• Huxtable , R. , Paplanus , M. D. and Laugharn , B. S. 1977 . The prevention of monocrotaline‐induced right ventricular hypertrophy . Chest , 71 (2) : 308 – 310 . (suppl.)
   PubMed Web of Science ®Google Scholar
• Huxtable , R. J. , Ciaramitaro , D. and Eisenstein , D. 1978 . The effects of a pyrrolizidine alkaloid, monocrotaline, and a pyrrole, dehydroretronecine, on the biochemical functions of the pulmonary endothelium . Mol. Pharmacol. , 14 : 1189 – 1203 .
   PubMed Web of Science ®Google Scholar
• Ichikawa , K. I. , Hidai , C. , Okuda , C. , Kimata , S. I. , Matsuoka , R. , Hosoda , S. , Quertermous , T. and Kawana , M. 1996 . Endogenous endothelin‐1 mediates cardiac hypertrophy and switching of myosin heavy chain gene expression in rat ventricular myocardium . J. Am. Coll. Cardiol. , 27 : 1286 – 1291 .
   PubMedGoogle Scholar
• Inglesby , T. V. , Singer , J. W. and Cordon , D. S. 1973 . Abnormal fibrinolysis in familial pulmonary hypertension . Am. J. Med. , 55 : 5 – 14 .
   PubMedGoogle Scholar
• Inoue , M. , Watanabe , K. , Mori , C. and Tanaka , O. 1994 . The effect of bunazosin on monocrotaline‐induced pulmonary hypertension in rats . Acta Paediatr. Jpn. , 36 : 133 – 138 .
   PubMedGoogle Scholar
• International Agency for Research in Cancer . 1976 . Monocrotaline . IARC Monogr. Eval. Carcinogen. Risk Chem. Man , 10 : 265 – 342 .
   PubMedGoogle Scholar
• Ishikawa , K. , Hashimoto , H. , Mitani , S. , Toki , Y. , Okumura , K. and Ito , T. 1995 . Enalapril improves heart failure induced by monocrotaline without reducing pulmonary hypertension in rats: Roles of preserved myocardial creatine kinase and lactate dehydrogenase isoenzymes . Int. J. Cardiol. , 6 : 225 – 233 .
   Google Scholar
• Ito , K. , Nakashima , T. , Murakami , K. and Murakami , T. 1988 . Altered function of pulmonary endothelium following monocrotaline‐induced lung vascular injury in rats . Br. J. Pharmacol. , 94 : 1175 – 1183 .
   PubMedGoogle Scholar
• Iwasawa , Y. , Gillis , C. N. and Aghajanian , G. 1973 . Hypothermic inhibition of 5‐hydroxytryptamine and norepinephrine uptake by lung: Cellular location of amines after uptake . J. Pharmacol. Exp. Ther. , 186 : 498 – 507 .
   PubMedGoogle Scholar
• Jackson , C. M. and Nemerson , Y. 1980 . Blood coagulation . Annu. Rev. Biochem. , 49 : 765 – 811 .
   PubMed Web of Science ®Google Scholar
• Jaffe , E. A. 1983 . “ Vascular function in hemostasis ” . In Hematology, , 3rd ed. , Edited by: Williams , W. J. , Beutler , E. , Erslev , A. J. and Lichtman , M. A. 1277 – 1287 . New York : McGraw‐Hill .
   Google Scholar
• Jaffe , E. A. 1987 . Cell biology of endothelial cells . Hum. Pathol. , 18 : 234 – 239 .
   PubMed Web of Science ®Google Scholar
• Jones , P. L. and Rabinovitch , M. 1996 . Tenascin‐C is induced with progressive pulmonary vascular disease in rats and is functionally related to increased smooth muscle cell proliferation . Circ. Res. , 79 : 1131 – 1142 .
   PubMed Web of Science ®Google Scholar
• Kameji , R. , Otsuka , H. and Hayashi , Y. 1980 . Increase of collagen synthesis in pulmonary arteries of monocrotaline‐treated rats . Experientia , 36 : 441 – 442 .
   PubMedGoogle Scholar
• Kanai , Y. , Hori , S. , Tanaka , T. , Yasuoka , M. , Watanabe , K. , Aikawa , N. and Hosoda , Y. 1993 . Role of 5‐hydroxytryptamine in the progression of monocrotaline induced pulmonary hypertension in rats . Cardiovasc. Res. , 27 : 1619 – 1623 .
   PubMed Web of Science ®Google Scholar
• Kasahara , Y. , Tatsumi , K. , Nakano , H. , Sugito , K. , Igari , H. , Saito , T. and Kuriyama , T. 1995 . The induction of inducible nitric oxide synthase in rat lungs with pulmonary hypertension (abstr.) . Am. J. Respir. Crit. Care Med. , 151 : A728
   Google Scholar
• Kasselberg , A. G. , Orth , D. N. , Gray , M. E. and Stahman , M. T. 1985 . Immunocytochemical localization of human epidermal growth factor/urogastrone in several human tissues . J. Histochem. Cytochem. , 33 : 315 – 322 .
   PubMed Web of Science ®Google Scholar
• Kasturi , T. E. , Manchanda , S. C. , Tandon , R. K. , Rajani , M. and Bhatia , M. L. 1979 . Haemodynamic studies in venoocclusive disease of the liver . Br. Heart J. , 41 : 594 – 599 .
   PubMedGoogle Scholar
• Katayama , Y. , Hatanaka , K. , Hayashi , T. , Onoda , K. , Yada , I. , Namikawa , S. , Yuasa , H. , Kusagawa , M. , Maruyama , K. and Kitabatake , M. 1994 . Effects of inhaled nitric oxide in rats with chemically induced pulmonary hypertension . Respir. Physiol. , 97 : 301 – 307 .
   PubMedGoogle Scholar
• Kay , J. M. and Heath , D. 1966 . Observations on the pulmonary arteries and heart weight of rats fed on Crotalaria spectabilis seeds . J. Pathol. Bacteriol. , 92 : 385 – 394 .
   PubMedGoogle Scholar
• Kay , J. M. and Heath , D. 1969 . Crotalaria spectabilis—The pulmonary hypertension plant , 5 – 11 . 62 – 95 . 99 – 110 . Springfield, IL : Charles C. Thomas .
   Google Scholar
• Kay , J. M. , Smith , P. and Heath , D. 1969 . Electron microscopy of Crotalaria pulmonary hypertension . Thorax , 24 : 511 – 526 .
   PubMed Web of Science ®Google Scholar
• Kay , J. M. , Suyama , K. L. and Keane , P. M. 1982a . Failure to show decrease in small pulmonary blood vessels in rats with experimental pulmonary hypertension . Thorax , 37 : 927 – 930 .
   PubMedGoogle Scholar
• Kay , J. M. , Keane , P. M. , Suyama , K. L. and Gauthier , D. 1982b . Angiotensin converting enzyme activity and evolution of pulmonary vascular disease in rats with monocrotaline pulmonary hypertension . Thorax , 37 : 88 – 96 .
   PubMed Web of Science ®Google Scholar
• Keane , P. M. and Kay , J. M. 1984 . Lung angiotensin converting enzyme activity in monocrotaline pulmonary hypertension (letter) . Thorax , 39 : 159
   PubMedGoogle Scholar
• Keane , P. M. , Kay , J. M. , Suyama , K. L. , Gauthier , D. and Andrew , K. 1982 . Lung angiotensin converting enzyme activity in rats with pulmonary hypertension . Thorax , 37 : 198 – 204 .
   PubMedGoogle Scholar
• Keski‐Oja , J. , Leof , E. B. , Lyons , R. M. , Coffey , R. J. and Moses , H. L. 1987 . Transforming growth factors and control of neoplastic cell growth . J. Cell. Biochem. , 33 : 95 – 107 .
   PubMed Web of Science ®Google Scholar
• King , A. , Smith , P. and Heath , D. 1994 . Ultrastructural differences between pulmonary arteriolar muscularization induced by hypoxia and monocrotaline . Exp. Mol. Pathol. , 61 : 24 – 35 .
   PubMedGoogle Scholar
• Kingdon , H. S. , Cohen , L. S. , Roberts , W. C. and Braunwald , E. 1966 . Familial occurrence of primary pulmonary hypertension . Arch. Intern. Med. , 118 : 422 – 426 .
   PubMedGoogle Scholar
• Kreutz , R. , Fernandez‐Alfonso , M.S. , Ganten , D. and Paul , M. 1996 . Effect of losarían on right ventricular hypertrophy and cardiac angiotensin l‐converting enzyme activity in pulmonary hypertensive rats . Clin. Exp. Hypertens. , 18 : 101 – 111 .
   PubMed Web of Science ®Google Scholar
• Krishnamurti , C. and Alving , B. M. 1992 . Plasminogen activator inhibitor type 1: Biochemistry and evidence for modulation of fibrinolysis in vivo . Semin. Thromb. Hemostasis , 18 : 67 – 80 .
   PubMed Web of Science ®Google Scholar
• Kuo , P. C. and Schroeder , R. A. 1994 . The emerging multifaceted roles of nitric oxide . Ann. Surg , 221 : 230 – 235 .
   Google Scholar
• Lafranconi , W. M. and Huxtable , R. J. 1983 . Changes in angiotensin‐converting enzyme activity in lungs damaged by the pyrrolizidine alkaloid monocrotaline . Thorax , 38 : 307 – 309 .
   PubMedGoogle Scholar
• Lafranconi , W. M. , Duhamel , R. C. , Brendel , K. and Huxtable , R. J. 1984 . Differentiation of the cardiac and pulmonary toxicity of monocrotaline, a pyrrolizidine alkaloid . Biochem. Pharmacol. , 33 : 191 – 197 .
   PubMedGoogle Scholar
• Lafranconi , W. M. , Ohkuma , S. and Huxtable , R. J. 1985 . Biliary excretion of novel pneumotoxic metabolites of the pyrrolizidine alkaloid, monocrotaline . Toxicon , 23 : 983 – 992 .
   PubMedGoogle Scholar
• Lai , Y. L. and Zhou , K. R. 1997 . Eglin‐c prevents monocrotaline‐induced ventilatory dysfunction . J. Appl. Physiol. , 82 : 324 – 328 .
   PubMedGoogle Scholar
• Lai , Y. L. , Olson , J. W. and Gillespie , M. N. 1991 . Ventilatory dysfunction precedes pulmonary vascular changes in monocrotaline‐treated rats . J. Appl. Physiol. , 70 : 561 – 566 .
   PubMedGoogle Scholar
• Lai , Y. L. , Thacker , A. A. and Diana , J. N. 1996 . Hypoxemia and elevated tachykinins in rat monocrotaline pneumotoxicity . Lung , 174 : 195 – 203 .
   PubMedGoogle Scholar
• Lalich , J. J. and Ehrhart , L. A. 1962 . Monocrotaline‐induced pulmonary arteritis in rats . J. Atheroscler. Res. , 2 : 482 – 492 .
   PubMedGoogle Scholar
• Lalich , J. J. , Johnson , W. D. , Raczniak , T. F. and Shumaker , R. C. 1977 . Fibrin thrombosis in monocrotaline pyrrole‐induced cor pulmonale in rats . Arch. Pathol. Lab. Med. , 101 : 69 – 73 .
   PubMedGoogle Scholar
• Lalich , J. J. and Merkow , L. 1961 . Pulmonary arteritis produced in rats by feeding Crotalaria spectabilis . Lab. Invest. , 10 : 744 – 750 .
   PubMed Web of Science ®Google Scholar
• Lame , M. W. , Morin , D. , Jones , A. D. , Segall , H. J. and Wilson , D. W. 1990 . Isolation and identification of a pyrrolic glutathione conjugate metabolite of the pyrrolizidine alkaloid, monocrotaline . Toxicol. Lett. , 51 : 321 – 329 .
   PubMed Web of Science ®Google Scholar
• Lame , M. W. , Jones , A. D. , Morin , D. and Segall , H. J. 1991 . Metabolism of [14C]monocrotaline by isolated perfused rat liver . Drug Metab. Dispos. , 19 : 516 – 524 .
   PubMed Web of Science ®Google Scholar
• Lame , M. W. , Jones , A. D. , Morin , D. , Wilson , D. W. and Segall , H. J. 1997 . Association of dehydromonocrotaline with rat red blood cells . Chem. Res. Toxicol. , 10 : 694 – 701 .
   PubMedGoogle Scholar
• Langleben , D. and Reid , L. 1985 . Effect of methylprednisolone on monocrotaline‐induced pulmonary vascular disease and right ventricular hypertrophy . Lab. Invest. , 52 : 298 – 303 .
   PubMedGoogle Scholar
• Langleben , D. , Carvalho , A. C. A. and Reid , L. M. 1986 . The platelet thromboxane inhibitor, dazmegrel, does not reduce monocrotaline‐induced pulmonary hypertension . Am. Rev. Respir. Dis. , 133 : 789 – 791 .
   PubMedGoogle Scholar
• Langleben , D. , Szarek , J. L. , Coflesky , J. T. , Jones , R. C. , Reid , L. M. and Evans , J. N. 1988 . Altered artery mechanics and structure in monocrotaline pulmonary hypertension . J. Appl. Physiol. , 65 : 2326 – 2331 .
   PubMedGoogle Scholar
• Lappin , P. B. and Roth , R. A. 1997 . Hypertrophy and prolonged DNA synthesis in smooth muscle cells characterize pulmonary arterial wall thickening after monocrotaline pyrrole administration to rats . Toxicol. Pathol. , 25 : 372 – 380 .
   PubMedGoogle Scholar
• Lappin , P. B. , Ross , K. L. , King , L. E. , Fraker , P. J. and Roth , R. A. 1998 . The response of pulmonary vascular endothelial cells to monocrotaline pyrrole: cell proliferation and DNA synthesis in vitro and in vivo . Toxicol. Appl. Pharmacol. , 150 : 37 – 48 .
   PubMedGoogle Scholar
• Levin , E. G. and Santell , L. 1987 . Conversion of the active to latent plasminogen activator inhibitor from human endothelial cells . Blood , 70 : 1090 – 1098 .
   PubMedGoogle Scholar
• Levine , J. D. , Harlan , J, M. , Harker , L. A. , Joseph , M. L. and Counts , R. B. 1982 . Thrombin‐mediated release of factor VIII antigen from human umbilical vein endothelial cells in culture . Blood , 60 : 531 – 534 .
   PubMed Web of Science ®Google Scholar
• Lichey , J. , Friedrich , T. , Franke , J. , Nigam , S. , Priesnitz , M. and Oeff , K. 1984 . Pressure effects and uptake of platelet‐activating factor in isolated rat lung . J. Appl. Physiol. , 57 : 1039 – 1044 .
   PubMedGoogle Scholar
• Lipke , D. W. , Arcot , S. S. , Cillespie , M. N. and Olson , J. W. 1993 . Temporal alterations in specific basement membrane components in lungs from monocrotaline‐treated rats . Am. J. Respir. Cell. Mol. Biol. , 9 : 418 – 428 .
   PubMed Web of Science ®Google Scholar
• Lipke , D. L. , Aziz , S. M. , Fagerland , J. A. , Majesky , M. and Arcot , S. S. 1996 . Tenascin synthesis, deposition, and isoforms in monocrotaline‐induced pulmonary hypertensive rat lungs . Am. J. Physiol. , 271 (2 pt. 1) : L208 – L215 .
   Web of Science ®Google Scholar
• Loskutoff , D. J. 1988 . Type 1 plasminogen activator inhibitor and its potential influence on thrombolytic therapy . Semin. Thromb. Hemostasis , 14 : 100 – 109 .
   PubMedGoogle Scholar
• Madden , J. A. , Keller , P. A. , Effros , R. M. , Seavitte , C. , Choy , J. S. and Hacker , A. D. 1994 . Responses to pressure and vasoactive agents by isolated pulmonary arteries from monocrotaline‐treated rats . J. Appl. Physiol. , 76 : 1589 – 1593 .
   PubMedGoogle Scholar
• Madden , J. A. , Keller , P. A. , Choy , J. S. , Alvarez , T. A. and Hacker , A. D. 1995 . L‐Arginine‐related responses to pressure and vasoactive agents in monocrotaline‐treated rat pulmonary arteries . J. Appl. Physiol. , 79 : 589 – 593 .
   PubMedGoogle Scholar
• Mansoor , A. M. , Honda , M. , Saida , K. , Ishinaga , Y. , Kuramochi , T. , Maeda , A. , Takabatake , T. and Mitsui , Y. 1995 . Endothelin induced collagen remodeling in experimental pulmonary hypertension . Biochem. Biophys. Res. Commun. , 215 : 981 – 986 .
   PubMed Web of Science ®Google Scholar
• Marcum , J. A. and Rosenberg , R. D. 1988 . “ The biochemistry and physiology of anticoagulantly active heparin‐like molecules ” . In Endothelial cell biology in health and disease , Edited by: Simionescu , N. and Simionescu , M. 207 – 228 . New York : Plenum Press .
   Google Scholar
• Marshall , B. E. and Marshall , C. 1991 . “ Pulmonary hypertension ” . In The lung , Edited by: Crystal , R. G. and West , J. B. 1177 – 1187 . New York : Raven Press .
   Google Scholar
• Maruyama , I. , Salem , H. H. and Majerus , P. W. 1984 . Coagulation factor Va binds to human umbilical vein endothelial cells and accelerates protein C activation . J. Clin. Invest. , 74 : 224 – 230 .
   PubMedGoogle Scholar
• Maruyama , K. , Kitabatake , M. , Maruyama , J. , Yamauchi , T. , Muneyuki , M. and Miyasaka , K. 1995 . The effect of continuous inhalation of nitric oxide on monocrotaline‐induced pulmonary hypertension and pulmonary vascular changes (abstr.) . Am. J. Respir. Crit. Care Med. , 151 : A730
   Google Scholar
• Maruyama , J. , Maruyama , K. , Mitani , Y. , Kitabatake , M. , Yamauchi , T. and Miyasaka , K. 1997 . Continuous low‐dose NO inhalation does not prevent monocrotaline‐induced pulmonary hypertension in rats . Am. J. Physiol. , 272 (1 pt. 2) : H517 – H524 .
   Web of Science ®Google Scholar
• Masugi , Y. , Oami , H. , Aihara , K. , Hashimoto , K. and Hakozaki , T. 1965 . Renal and pulmonary vascular changes induced by Crotalaria spectabilis in rats . Acta Pathol. Jpn. , 15 : 407 – 415 .
   PubMedGoogle Scholar
• Mathew , R. , Guzowski , D. E. and Gloster , E. S. 1990 . Effect of verapamil on monocrotaline‐induced pulmonary artery hypertension and endothelial cell dysfunction in rats . Exp. Lung Res. , 16 : 627 – 644 .
   PubMed Web of Science ®Google Scholar
• Mathew , R. , Zeballos , G. A. , Tun , H. and Gewitz , M. H. 1995 . Role of nitric oxide and endothelin‐1 in monocrotaline‐induced pulmonary hypertension in rats . Cardiovasc. Res. , 30 : 739 – 746 .
   PubMed Web of Science ®Google Scholar
• Mathew , R. , Gloster , E. S. , Sundararajan , T. , Thompson , C. I. , Zeballos , G. A. and Gewitz , M. H. 1997 . Role of inhibition of nitric oxide production in monocrotaline‐induced pulmonary hypertension . J. Appl. Physiol. , 82 : 1493 – 1498 .
   PubMed Web of Science ®Google Scholar
• Mattocks , A. R. 1972 . Acute hepatotoxicity and pyrrolic metabolites in rats dosed with pyrrolizidine alkaloids . Chew. Biol. Interact. , 5 : 227 – 242 .
   PubMed Web of Science ®Google Scholar
• Mattocks , A. R. 1986 . “ Metabolism, distribution and excretion of pyrrolizidine alkaloids ” . In Chemistry and toxicology of pyrrolizidine alkaloids , 158 – 190 . London : Academic Press .
   Google Scholar
• Mattocks , A. R. and Jukes , R. 1990 . Trapping and measurement of short‐lived alkylating agents in a recirculating flow system . Chem. Biol. Interact. , 76 : 19 – 30 .
   PubMedGoogle Scholar
• Mattocks , A. R. and White , I. N. H. 1970 . Estimation of metabolites of pyrrolizidine alkaloids in animal tissues . Anal. Biochem. , 38 : 529 – 535 .
   PubMed Web of Science ®Google Scholar
• Mattocks , A. R. and White , I. N. H. 1971 . The conversion of pyrrolizidine alkaloids to N‐oxides and to dihydropyrrolizine derivatives by rat liver microsomes in vitro . Chem. Biol. Interact. , 3 : 383 – 396 .
   PubMed Web of Science ®Google Scholar
• Mattocks , A. R. , Legg , R. F. and Jukes , R. 1990 . Trapping of short‐lived electrophile metabolites of pyrrolizidine alkaloids escaping from perfused rat liver . Toxicol. Lett. , 54 : 93 – 99 .
   PubMedGoogle Scholar
• McFarlane , A. L. and Branday , W. J. 1945 . Hepatic enlargement with ascites in children . Br. Med. J. , 1 : 838 – 840 .
   PubMed Web of Science ®Google Scholar
• McLean , E. K. 1970 . Toxic actions of pyrrolizidine (Senecio) alkaloids . Pharmacol. Rev. , 22 : 429 – 483 .
   PubMedGoogle Scholar
• McLeod , A. A. and Jewitt , D. E. 1986 . Drug treatment of primary pulmonary hypertension . Drugs , 31 : 177 – 184 .
   PubMedGoogle Scholar
• McNabb , L. J. and Baldwin , K. M. 1984 . Hemodynamic and metabolic effects of exercise in Crotalaria‐induced pulmonary hypertension in rats . J. Appl. Physiol. Respir. Environ. Exercise Physiol. , 57 : 1829 – 1833 .
   PubMedGoogle Scholar
• Merkow , L. and Kleinerman , J. 1966 . An electron microscopic study of pulmonary vasculitis induced by monocrotaline . Lab. Invest. , 15 : 547 – 564 .
   PubMed Web of Science ®Google Scholar
• Meyrick , B. and Brigham , K. L. 1986 . Repeated f. coli endotoxin induced pulmonary inflammation causes chronic pulmonary hypertension in sheep: Structural and functional changes . Lab. Invest. , 55 : 164 – 176 .
   PubMedGoogle Scholar
• Meyrick , B. and Reid , L. 1979a . Development of pulmonary arterial changes in rats fed Crotalaria spectabilis . Am. J. Pathol. , 94 : 37 – 50 .
   PubMed Web of Science ®Google Scholar
• Meyrick , B. and Reid , L. 1979b . Hypoxia and incorporation of 3H‐thymidine by cells of rat pulmonary arteries and alveolar wall . Am. J. Pathol. , 96 : 51 – 70 .
   PubMed Web of Science ®Google Scholar
• Meyrick , B. O. and Reid , L. M. 1982 . Crotalaria‐induced pulmonary hypertension. Uptake of 3H‐thymidine by cells of the pulmonary circulation and alveolar walls . Am. J. Pathol. , 106 : 84 – 94 .
   PubMed Web of Science ®Google Scholar
• Meyrick , B. , Gamble , W. and Reid , L. 1980 . Development of Crotalaria pulmonary hypertension: Hemodynamic and structural study . Am. J. Physiol. , 239 : H692 – H702 . (Heart Circ. Physiol. 8)
   PubMed Web of Science ®Google Scholar
• Meyrick , B. , Niedermeyer , M. E. , Ogletree , M. L. and Brigham , K. L. 1985 . Pulmonary hypertension and increased pulmonary vasoreactivity caused by repeated indomethacin in sheep . J. Appl. Physiol. , 59 : 443 – 452 .
   PubMedGoogle Scholar
• Meyrick , B. , Perkett , E. A. and Brigham , K. L. 1987 . Inflammation and models of chronic pulmonary hypertension . Am. Rev. Respir. Dis. , 136 : 767 – 769 .
   PubMedGoogle Scholar
• Miller , W. C. , Rice , D. L. , Kreusel , R. G. and Bedrossian , C. W. M. 1978 . Monocrotaline model of noncardiogenic pulmonary edema in dogs . J. Appl. Physiol. Respir. Environ. Exercise Physiol. , 45 : 962 – 965 .
   PubMedGoogle Scholar
• Miller , W. C. , Rice , D. L. , linger , K.M. and Bradley , B. L. 1981 . Effect of PEEP on lung water content in experimental noncardiogenic pulmonary edema . Crit. Care Med. , 9 : 7 – 9 .
   PubMedGoogle Scholar
• Miyata , M. , Ueno , Y. , Sekine , H. , Ito , O. , Sakuma , F. , Koike , H. , Nishio , S. , Nishimaki , T. and Kasukawa , R. 1996 . Protective effect of beraprost sodium, a stable prostacyclin analogue, in development of monocrotaline‐induced pulmonary hypertension . J. Cardiovasc. Pharmacol. , 27 : 20 – 26 .
   PubMedGoogle Scholar
• Miyauchi , T. , Yorikane , R. , Sakai , S. , Sakurai , T. , Okada , M. , Nishikibe , M. , Yano , M. , Yamaguchi , I. , Sugishita , Y. and Goto , K. 1993 . Contribution of endogenous endothelin‐1 to the progression of cardiopulmonary alterations in rats with monocrotaline‐induced pulmonary hypertension . Circ. Res. , 73 : 887 – 897 .
   PubMed Web of Science ®Google Scholar
• Mojarad , M. , Hamasaki , Y. and Said , S. I. 1983 . Platelet‐activating factor increases pulmonary microvascular permeability and induces pulmonary edema . Bull. Eur. Physiopathol. Respir. , 19 : 253 – 256 .
   PubMedGoogle Scholar
• Molteni , A. , Ward , W. F. , Ts'ao , C.H. , Port , C. D. and Solliday , N. H. 1984 . Monocrotaline‐induced pulmonary endothelial dysfunction in rats . Proc. Soc. Exp. Biol. Med. , 176 : 88 – 94 .
   PubMedGoogle Scholar
• Molteni , A. , Ward , W. F. , Ts'ao , C.H. , Solliday , N. H. and Dunne , M. 1985 . Monocrotaline‐induced pulmonary fibrosis in rats: Amelioration by captopril and penicillamine . Proc. Soc. Exp. Biol. Med. , 180 : 112 – 120 .
   PubMed Web of Science ®Google Scholar
• Molteni , A. , Ward , W. F. , Ts'ao , C.H. and Solliday , N. H. 1986a . Modification of monocrotaline‐induced pulmonary injury by angiotensin converting enzyme inhibitors CGS13945 and CGS16617 . Fed Proc. , 45 : 461
   Google Scholar
• Molteni , A. , Ward , W. F. , Ts'ao , C.H. and Solliday , N. H. 1986b . Monocrotaline‐induced cardiopulmonary damage in rats: Amelioration by the angiotensin‐converting enzyme inhibitor CL242817 . Proc. Soc. Exp. Biol. Med. , 182 : 483 – 493 .
   PubMed Web of Science ®Google Scholar
• Molteni , A. , Ward , W. F. , Ts'ao , C. and Solliday , N. H. 1987 . Monocrotaline‐induced cardiopulmonary injury in rats: Modification by thiol and nonthiol ACE inhibitors . Clin. Exp. Theory Pract. , A9 (2 & 3) : 381 – 385 .
   Google Scholar
• Molteni , A. , Ward , W. F. , Ts'ao , C.H. and Fitzsimons , E. J. 1988a . Serum copper concentration as an index of cardiopulmonary injury in monocrotaline‐treated rats . Ann. Clin. Lab. Sci. , 18 : 476 – 483 .
   PubMedGoogle Scholar
• Molteni , A. , Ward , W. F. , Ts'ao , C. and Solliday , N. H. 1988b . Monocrotaline‐induced cardiopulmonary injury in rats: modification by the nonthiol ACE inhibitors CGS13945 and CGS16617 . Arch. Int. Pharmacodyn. Ther. , 291 : 21 – 39 .
   PubMedGoogle Scholar
• Molteni , A. , Ward , W. F. , Ts'ao , C.H. and Hinz , J. M. 1989 . Monocrotaline‐induced cardiopulmonary injury in rats. Modification by the neutrophil elastase inhibitor SC39026 . Biochem. Pharmacol. , 38 : 2411 – 2419 .
   PubMedGoogle Scholar
• Morel , D. R. , Dargent , F. , Bachmann , M. , Suter , P. M. and Junrod , A. F. 1985 . Pulmonary extraction of serotonin and propranolol in patients with adult respiratory distress syndrome . Am. Rev. Respir. Dis. , 132 : 479 – 484 .
   PubMedGoogle Scholar
• Morita , K. , Ogawa , Y. and Tobise , K. 1996 . Effect of endothelium of pulmonary artery vasoreactivity in monocrotaline‐induced pulmonary hypertensive rats . Jpn. Circ. J. , 60 : 585 – 592 .
   PubMedGoogle Scholar
• Mroczkowski , B. and Ball , R. 1990 . “ Epidermal growth factor: Biology and properties of its gene and protein precursor ” . In Growth factors, differentiation factors, and cytokines , Edited by: Habenicht , A. 18 – 30 . Berlin : Springer‐Verlag .
   Google Scholar
• Nawroth , P. P. and Stem , D. M. 1986 . “ Endothelial cells as active participants in coagulation reactions ” . In Vascular endothelium in haemostasis and thrombosis , Edited by: Gimbrone , M. A. 14 – 39 . Edinburgh : Churchill Livingstone .
   Google Scholar
• Nawroth , P. P. , Handley , D. and Stern , D. M. 1986 . The multiple levels of endothelial cell‐coagulation factor interactions . Clin. Haematol. , 15 : 293 – 321 .
   PubMedGoogle Scholar
• Nemerson , Y. 1988 . Tissue factor and hemostasis . Blood , 71 : 1 – 8 .
   PubMed Web of Science ®Google Scholar
• Newberne , P. M. , Wilson , R. and Rogers , A. E. 1971 . Effects of a low‐lipotrope diet on the response of young male rats to the pyrrolizidine alkaloid, monocrotaline . Toxicol. Appl. Pharmacol. , 18 : 387 – 397 .
   PubMed Web of Science ®Google Scholar
• Ng , K. K. F. and Vane , J. R. 1967 . Conversion of angiotensin I to angiotensin II . Nature , 216 : 762 – 766 .
   PubMed Web of Science ®Google Scholar
• Nilsson , J. , Sjolund , M. , Palmberg , L. , Thyberg , J. and Heldin , C. H. 1985 . Arterial smooth muscle cells in primary culture produce a platelet‐derived growth factor‐like protein . Proc. Natl. Acad. Sci. USA , 82 : 4418 – 4422 .
   PubMed Web of Science ®Google Scholar
• Oehlenschlager , W. F. , Kurtz , D. T. , Baron , D. A. and Currie , M. C. 1989 . Enhanced activity of the cardiac endocrine system during right ventricular hypertrophy . Mol. Cell. Endocrinol. , 62 : 243 – 251 .
   PubMedGoogle Scholar
• Ohie , T. , Kikuchi , K. , Watanabe , K. and Mori , C. 1993 . Cardiac atrial natriuretic peptide in monocrotaline‐induced pulmonary hypertensive rats . Acta Paediatr. Jpn. , 35 : 278 – 282 .
   PubMedGoogle Scholar
• Oka , Y. and Orth , D. N. 1983 . Human plasma epidermal growth factor/B‐urogastrone is associated with blood platelets . J. Clin. Invest. , 72 : 249 – 259 .
   PubMed Web of Science ®Google Scholar
• Okada , M. , Yamashita , C. , Okada , M. and Okada , K. 1995a . A dehydromonocrotaline‐induced pulmonary hypertension model in the beagle . J. Thorac. Cardiovasc. Surg. , 110 : 546 – 547 .
   PubMed Web of Science ®Google Scholar
• Okada , M. , Yamashita , C. , Okada , M. and Okada , K. 1995b . Endothelin receptor antagonists in a beagle model of pulmonary hypertension: Contribution to possible potential therapy? . J. Am. Coll. Cardiol. , 25 : 1213 – 1217 .
   PubMed Web of Science ®Google Scholar
• Okumura , K. , Kondo , J. , Shimizu , K. , Yoshino , M. , Toki , Y. , Hashimoto , H. and Ito , T. 1992 . Changes in ventricular 1,2‐diacylglycerol content in rats following monocrotaline treatment . Cardiovasc. Res. , 26 : 626 – 630 .
   PubMedGoogle Scholar
• Ono , S. and Voelkel , N. F. 1991 . PAF antagonists inhibit monocrotaline‐induced lung injury and pulmonary hypertension . J. Appl. Physiol. , 71 : 2483 – 2492 .
   PubMed Web of Science ®Google Scholar
• Ono , S. and Voelkel , N. F. 1992 . PAF receptor blockade inhibits lung vascular changes in the rat monocrotaline model . Lung , 170 : 31 – 40 .
   PubMedGoogle Scholar
• Ono , S. , Tanita , T. , Asnino , Y. , Noda , M. , Tabata , S. , Hoshikawa , Y. , Ueda , S. , Nishimura , T. and Fujimura , S. 1994 . Lung 3H‐thymidine incorporation in monocrotaline (MCT)‐treated rats—Role of platelet‐activating factor (PAF) . Nippon Kyobu Shikkan Gakkai Zasshi , 32 : 441 – 445 .
   PubMedGoogle Scholar
• Page , C. P. , Archer , C. B. , Paul , W. and Morley , J. 1984 . Paf‐acether. A mediator of inflammation and asthma . Trends Pharmacol. Sci. , 5 : 239 – 241 .
   Web of Science ®Google Scholar
• Palevsky , H. I. and Fishman , A. P. 1985 . Vasodilator therapy for primary pulmonary hypertension . Annu. Rev. Med. , 36 : 563 – 578 .
   PubMedGoogle Scholar
• Palevsky , H. I. and Weiss , D. W. 1990 . Clinical pathologic conference. Pulmonary hypertension secondary to chronic thromboembolism . J. Nucl. Med. , 31 : 1 – 9 .
   PubMedGoogle Scholar
• Pan , L. E. , Lame , M. W. , Morin , D. , Wilson , D. W. and Segall , H. J. 1991 . Red blood cells augment transport of reactive metabolites of monocrotaline from liver to lung in isolated and tandem liver and lung preparations . Toxicol Appl. Pharmacol. , 110 : 336 – 346 .
   PubMedGoogle Scholar
• Pan , L. C. , Lame , M. W. , Wilson , D. W. and Segall , H. J. 1992 . Cor pulmonale is caused by putative monocrotaline metabolite MCTP, but not glutathione or cysteine conjugates . Toxicologist , 12 : 34
   Google Scholar
• Perkett , E. A. , Brigham , K. L. and Meyrick , B. 1986 . Increased vasoreactivity and chronic pulmonary hypertension following thoracic irradiation in sheep . J. Appl. Physiol. , 61 : 1875 – 1881 .
   PubMedGoogle Scholar
• Perkett , E. A. , Brigham , K. L. and Meyrick , B. 1988 . Continuous air embolization into sheep causes sustained pulmonary hypertension and increased pulmonary vasoreactivity . Am. J. Pathol. , 132 : 444 – 454 .
   PubMed Web of Science ®Google Scholar
• Plestina , R. and Stoner , H. B. 1972 . Pulmonary oedema in rats given monocrotaline pyrrole . J. Pathol. , 106 : 235 – 249 .
   PubMed Web of Science ®Google Scholar
• Preissner , K. T. 1988 . Anticoagulant potential of endothelial cell membrane components . Haemostasis , 18 : 271 – 306 .
   PubMedGoogle Scholar
• Rabinovitch , M. 1991 . Investigational approaches to pulmonary hypertension . Toxicol. Pathol. , 19 (4 pt. 1) : 458 – 469 .
   PubMed Web of Science ®Google Scholar
• Rabinovitch , M. , Gamble , W. , Nadas , A. S. , Miettinen , O. S. and Reid , R. L. 1976 . Rat pulmonary circulation after chronic hypoxia: Hemodynamic and structural features . Exp. Pathol. , 12 : 329 – 335 .
   Google Scholar
• Rabinovitch , M. , Andrew , M. , Thom , H. , Trusler , G. A. , Williams , W. G. , Rowe , R. D. and Olley , P. M. 1987 . Abnormal endothelial factor associated with pulmonary hypertension and congenital heart defects . Circulation , 766 : 1043 – 1052 .
   Google Scholar
• Raczniak , T. J. , Chesney , C. F. and Allen , J. R. 1978 . Ultrastructure of the right ventricle after monocrotaline‐induced cor pulmonale in the nonhuman primate (Macaca arctoides) . Exp. Mol. Pathol. , 28 : 107 – 118 .
   PubMedGoogle Scholar
• Raczniak , T. J. , Shumaker , R. C. , Allen , J. R. , Will , J. A. and Lalich , R. L. 1979 . Pathophysiology of dehydromonocrotaline‐induced pulmonary fibrosis in the beagle . Respiration , 37 : 252 – 260 .
   PubMedGoogle Scholar
• Rao , L. V. M. , Rapaport , S. I. and Lorenzi , M. 1987 . Enhancement by human umbilical vein endothelial cells of factor Xa‐catalyzed activation of factor VII . Blood , 71 : 791 – 796 .
   Google Scholar
• Rapaport , S. I. 1990 . “ The initiation of the tissue factor dependent pathway of blood coagulation ” . In Fibrinogen, thrombosis, coagulation, and fibrinolysis. Advances in experimental medicine and biology , Edited by: Liu , C. Y. and Chein , S. vol. 281 , 97 – 103 . New York : Plenum Press .
   Google Scholar
• Reeves , J. T. and Grover , B. M. 1985 . “ Approach to the patients with pulmonary hypertension ” . In Pulmonary hypertension , Edited by: Weir , E. K. and Reeves , J. T. 1 – 44 . New York : Futura .
   Google Scholar
• Reid , L. M. and Davies , P. 1989 . “ Control of cell proliferation in pulmonary hypertension ” . In Lung biology in health and vascular disease. Pulmonary vascular physiology and pathophysiology , Edited by: Weir , E. K. and Reeves , J. T. vol. 38 , 541 – 611 . New York : Marcel Dekker .
   Google Scholar
• Reid , L , Fried , R. , Geggel , R. and Langleben , D. 1986 . “ Anatomy of pulmonary hypertensive states ” . In Abnormal pulmonary circulation. Contemporary issues in pulmonary disease , Edited by: Bergosfsky , E. H. vol.4 , 221 – 263 . New York : Churchill Livingstone .
   Google Scholar
• Reindel , J. F. and Roth , R. A. 1991 . The effects of monocrotaline pyrrole on cultured bovine pulmonary artery endothelial and smooth muscle cells . Am. J. Pathol. , 138 : 707 – 719 .
   PubMedGoogle Scholar
• Reindel , J. F. , Ganey , P. E. , Wagner , J.G. , Slocombe , R. F. and Roth , R. A. 1990 . Development of morphologic, hemodynamic, and biochemical changes in lungs of rats given monocrotaline pyrrole . Toxicol. Appl. Pharmacol. , 106 : 179 – 200 .
   PubMed Web of Science ®Google Scholar
• Resta , T. C. , Gonzales , R. J. , Dail , W. G. , Sanders , T. C. and Walker , B. R. 1997 . Selective upregulation of arterial endothelial nitric oxide synthase in pulmonary hypertension . Am. J. Physiol. , 272 (2 pt. 2) : H806 – H813 .
   Web of Science ®Google Scholar
• Ribes , J. A. , Francis , C. W. and Wagner , D. D. 1987 . Fibrin induces release of von Willebrand factor from endothelial cells . J. Clin. Invest. , 79 : 117 – 123 .
   PubMed Web of Science ®Google Scholar
• Robbins , D. J. 1982 . “ The pyrrolizidine alkaloids ” . In Progress in the chemistry of organic natural products , Edited by: Herz , W. , Grisebach , H. and Kirby , G. W. 115 – 203 . Vienna : Springer‐Verlag .
   Google Scholar
• Rodgers , G. M. 1988 . Hemostatic properties of normal and perturbed vascular cells . FASEB J. , 2 : 116 – 123 .
   PubMed Web of Science ®Google Scholar
• Rose , A. L. , Gardner , C. A. , McConnell , D. and Bull , B. 1957 . Field and experimental investigation of “walk‐about” disease of horses (Kimberley horse disease) in northern Australia: Crotalaria poisoning in horses. Part II . Aust. Vet. J. , 33 : 49 – 62 .
   Google Scholar
• Rose , C. L. , Fink , R. D. , Harris , P. N. and Chen , K. K. 1945 . Effect of hepatotoxic alkaloids on prothrombin time of rats . J. Pharmacol. Exp. Ther. , 83 : 265 – 269 .
   Google Scholar
• Rosenberg , H. C. and Rabinovitch , M. 1988 . Endothelial injury and vascular reactivity in monocrotaline pulmonary hypertension . Am. J. Physiol. , 255 : H1484 – H1491 . (Heart Circ. Physiol. 24)
   PubMed Web of Science ®Google Scholar
• Ross , R. , Raines , E. W. and Bowen‐Pope , D. F. 1986 . The biology of platelet‐derived growth factor . Cell , 46 : 155 – 169 .
   PubMed Web of Science ®Google Scholar
• Roth , R. A. 1981 . Effect of pneumotoxicants on lactate dehydrogenase activity in the airways of rats . Toxicol. Appl. Pharmacol. , 57 : 69 – 78 .
   PubMed Web of Science ®Google Scholar
• Roth , R. A. 1985 . Biochemistry, physiology and drug metabolism—Implications regarding the role of the lung in drug disposition . Clin. Physiol. Biochem. , 3 : 66 – 79 .
   PubMedGoogle Scholar
• Roth , R. A. and Ganey , P. E. 1987 . Lipid mediators in the normal and abnormal pulmonary circulation. Arachidonic acid metabolites and mechanisms of monocrotaline pneumotoxicity . Am. Rev. Respir. Dis. , 136 : 762 – 765 .
   PubMedGoogle Scholar
• Roth , R. A. and Ganey , P. E. 1988 . Platelets and the puzzles of pulmonary pyrrolizidine poisoning . Toxicol. Appl. Pharmacol. , 93 : 463 – 471 .
   PubMedGoogle Scholar
• Roth , R. A. , Dotzlaf , L. A. , Baranyi , B. , Kuo , C.‐H. and Hook , J. B. 1981 . Effect of monocrotaline ingestion on liver, kidney, and lung of rats . Toxicol. Appl. Pharmacol. , 60 : 193 – 203 .
   PubMed Web of Science ®Google Scholar
• Roth , R. A. , White , S. M. and Reindel , J. F. 1989 . Mechanisms of lung injury and pulmonary hypertension from monocrotaline: An hypothesis . Comments Toxicol. , 3 : 131 – 144 .
   Google Scholar
• Ryan , J. W. , Ryan , U. S. , Shultz , D. R. , Whitaker , C. and Chung , A. 1975 . Subcellular localization of pulmonary angiotensin converting enzyme (Kinase II) . Biochem. J. , 146 : 497 – 499 .
   PubMed Web of Science ®Google Scholar
• Ryan , U. S. and Ryan , J. W. 1984 . Cell biology of pulmonary endothelium . Circulation , 70 (suppl. III) : III‐46 – III‐62 .
   Google Scholar
• Ryan , U. S. , Ryan , J. W. and Crutchley , D. J. 1985 . The pulmonary endothelial surface . Fed. Proc. , 44 : 2603 – 2609 .
   PubMedGoogle Scholar
• Rykerson , S. , Thompson , J. and Wessel , D. L. 1995 . Inhalation of nitric oxide: An innovative therapy for treatment of increased pulmonary vascular resistance . Nurs. Clin. North Am. , 30 : 381 – 390 .
   PubMedGoogle Scholar
• Ryland , D. and Reid , L. 1975 . The pulmonary circulation in cystic fibrosis . Thorax , 30 : 285 – 292 .
   PubMedGoogle Scholar
• Saksela , O. and Rifkin , D. B. 1988 . Cell‐associated plasminogen activation: regulation and physiological functions . Annu. Rev. Cell Biol. , 4 : 93 – 126 .
   PubMedGoogle Scholar
• Salido , E. C. , Barajas , L. , Lechago , J. , Laborde , N. and Fisher , D. A. 1986 . Immunocytochemical localization of epidermal growth factor in mouse kidney . J. Histochem. Cytochem. , 34 : 1155 – 1160 .
   PubMedGoogle Scholar
• Samson , W. K. 1985 . Atrial natriuretic factor inhibits dehydration and hemorrhage‐induced vasopressin release . Neuroendocrinology , 40 : 277 – 279 .
   PubMed Web of Science ®Google Scholar
• Sanders , D. A. , Shealy , A. L. and Emmel , M. W. 1936 . Crotalaria spectabilis (Roth) poisoning in cattle . J. Am. Vet. Med. Assoc. , 89 : 150 – 162 .
   Google Scholar
• Schmaier , A. H. , Kuo , A. and Cines , D. 1987 . High molecular weight kininogen expression on human endothelial cells . Clin. Res. , 35 : 432A
   Google Scholar
• Schembre , D. B. and Boynton , K. K. 1997 . Appetite‐suppressant drugs and primary pulmonary hypertension (letter) . N. Engl. J. Med. , 336 : 510 – 511 .
   PubMedGoogle Scholar
• Schoental , R. 1968 . Chemical structures and pathological effects of pyrrolizidine alkaloids . Is. J. Med. Sci. , 4 : 1133 – 1145 .
   PubMedGoogle Scholar
• Schoental , R. and Head , M. A. 1955 . Pathological changes in rats as a result of treatment with monocrotaline . Br. Cancer , 9 : 229 – 237 .
   Google Scholar
• Schraufnagel , D. E. and Schmid , A. 1989 . Pulmonary capillary density in rats given monocrotaline. A cast corrosion study . Am. Rev. Respir. Dis. , 140 : 1405 – 1409 .
   PubMedGoogle Scholar
• Schultze , A. E. and Roth , R. A. 1993a . Procoagulant and fibrinolytic properties of bovine endothelial cells treated with monocrotaline pyrrole . Toxicol. Appl. Pharmacol. , 122 : 7 – 15 .
   PubMedGoogle Scholar
• Schultze , A. E. and Roth , R. A. 1993b . Fibrinolytic activity in blood and lungs of rats treated with monocrotaline pyrrole . Toxicol. Appl. Pharmacol. , 121 : 129 – 137 .
   PubMedGoogle Scholar
• Schultze , A. E. , Wagner , J. G. , White , S. M. and Roth , R. A. 1991a . Early indications of monocrotaline pyrrole‐induced lung injury in rats . Toxicol. Appl. Pharmacol. , 109 : 41 – 50 .
   PubMedGoogle Scholar
• Schultze , A. E. , Wagner , J. G. and Roth , R. A. 1991b . An evaluation of procoagulant activity in the peripheral blood of rats treated with monocrotaline pyrrole . Toxicol. Appl. Pharmacol. , 109 : 421 – 431 .
   PubMedGoogle Scholar
• Schultze , A. E. , Gunaga , K. P. , Wagner , J. G. , Hoorn , C. M. , Moorehead , W. R. and Roth , R. A. 1994 . Total lactate dehydrogenase activity and isozyme patterns in tissues, cell lysates, and bronchoalveolar lavage fluid from rats treated with monocrotaline pyrrole . Toxicol. Appl. Pharmacol. , 126 : 301 – 310 .
   PubMed Web of Science ®Google Scholar
• Schultze , A. E. , Emeis , J. J. and Roth , R. A. 1996 . Cellular fibronectin and Von Willebrand factor concentrations in plasma of rats treated with monocrotaline pyrrole . Biochem. Pharmacol. , 51 : 187 – 191 .
   PubMedGoogle Scholar
• Selikoff , I. J. , Lee , D. H. K. Anderson , H. A. 1978 . Asbestos and disease , 25 – 30 . 143 – 188 . 207 – 240 . 413 – 416 . New York : Academic Press .
   Google Scholar
• Semmens , M. and Reid , L. 1974 . Pulmonary arterial muscularity and right ventricular hypertrophy in chronic bronchitis and emphysema . Br. J. Dis. Chest , 68 : 253 – 263 .
   PubMedGoogle Scholar
• Shubat , P. J. , Banner , W. and Huxtable , R. J. 1987 . Pulmonary vascular responses induced by the pyrrolizidine alkaloid, monocrotaline, in rats . Toxicon , 25 : 995 – 1002 .
   PubMedGoogle Scholar
• Simpson , C. F. , Waldroup , P. W. and Harms , R. H. 1963 . Pathologic changes associated with feeding various levels of Crotalaria spectabilis seed to poultry . J. Am. Vet Med. Assoc. , 142 : 264 – 271 .
   PubMedGoogle Scholar
• Smith , L. W. and Culvenor , C. C. J. 1981 . Plant sources of hepatotoxic pyrrolizidine alkaloids . J. Natl. Prod. , 44 : 129 – 152 .
   PubMed Web of Science ®Google Scholar
• Smith , P. and Heath , D. 1978 . Evagination of vascular smooth muscle cells during early stages of Crotalaria pulmonary hypertension . J. Pathol. , 124 : 177 – 183 .
   PubMedGoogle Scholar
• Snow , R. L. , Davies , P. , Pontoppidan , H. , Zapol , W. M. and Reid , L. 1982 . Pulmonary vascular remodeling in adult respiratory distress syndrome . Am. Rev. Respir. Dis. , 126 : 887 – 892 .
   PubMedGoogle Scholar
• Sprengers , E. D. and Kluft , C. 1987 . Plasminogen activator inhibitors . Blood , 69 : 381 – 387 .
   PubMed Web of Science ®Google Scholar
• Stenberg , P. E. and Bainton , D. F. 1986 . “ Storage organelles in platelets and megakaryocytes ” . In Biochemistry of platelets , Edited by: Phillips , D. R. and Shuman , M. A. 257 – 294 . Orlando, FL : Academic Press .
   Google Scholar
• Stenmark , K. R. , Morganroth , M. L. , Remigio , L. K. , Voelkel , N. F. , Murphy , R. C. , Hensen , P. M. , Mathias , M. M. and Reeves , J. T. 1985 . Alveolar inflammation and arachidonate metabolism in monocrotaline‐induced pulmonary hypertension . Am. J. Physiol. , 248 : H859 – H866 . (Heart Circ. Physiol. 17)
   PubMed Web of Science ®Google Scholar
• Stern , D. M. , Drillings , M. , Nossel , H. L. , Hurlet‐Jansen , A. , LaGamma , K. S. and Owen , J. 1983 . Binding of factors IX and IXa to cultured vascular endothelial cells . Proc. Natl. Acad. Sci. USA , 80 : 4119 – 4123 .
   PubMed Web of Science ®Google Scholar
• Stern , D. M. , Knitter , G. , Kisiel , W. and Nawroth , P. P. 1987 . In vivo evidence of intravascular binding sites for coagulation factor IX . Br. J. Haematol. , 66 : 227 – 232 .
   PubMedGoogle Scholar
• Stern , D. M. , Handley , D. A. and Nawroth , P. P. 1988a . “ Endothelium and the regulation of coagulation ” . In Endothelial cell biology in health and disease , Edited by: Simionescu , N. and Simionescu , M. 275 – 306 . New York : Plenum Press .
   Google Scholar
• Stem , D. M. , Kaiser , E. and Nawroth , P. P. 1988b . Regulation of the coagulation system by vascular endothelial cells . Haemostasis , 18 : 202 – 214 .
   PubMedGoogle Scholar
• Strum , J. M. and Junrod , A. F. 1972 . Autoradiographic demonstration of 5‐hydroxytryptamine‐'H uptake by pulmonary endothelial cells . J. Cell Biol. , 54 : 456 – 467 .
   PubMed Web of Science ®Google Scholar
• Sugita , T. , Stenmark , K. R. , Wagner , W. W. , Hensen , P. , Hensen , J. , Hyers , T. M. and Reeves , J. T. 1983 . Abnormal alveolar cells in monocrotaline induced pulmonary hypertension . Exp. Lung Res. , 5 : 201 – 215 .
   PubMed Web of Science ®Google Scholar
• Sunderman , F. W. and Leibman , K. C. 1970 . Nickel carbonyl inhibition of induction of aminopyrine demethylase activity in liver and lung . Cancer Res. , 30 : 1645 – 1650 .
   PubMed Web of Science ®Google Scholar
• Suttorp , N. , Seeger , W. , Uhl , J. , Lutz , F. and Roka , L. 1985 . Pseudomonas aeruginosa cytotoxin stimulates prostacyclin production in cultured pulmonary artery endothelial cells: Membrane attack and calcium influx . J. Cell. Physiol. , 123 : 64 – 72 .
   PubMedGoogle Scholar
• Tabrizchi , R. , MacNicol , B. M. and Lin , B. P. 1995 . Effects of calcium channel antagonists and pertussis toxin on noradrenaline‐induced contractions in pulmonary artery from pulmonary hypertensive rats . Life Sci. , 56 : 1173 – 1185 .
   PubMedGoogle Scholar
• Takada , A. , Urano , T. and Takada , Y. 1990 . “ The regulation of the activation of the fibrinolytic system ” . In Fibrinogen, thrombosis, coagulation, and fibrinolysis. Advances in experimental medicine and biology , Edited by: Liu , C. Y. and Chein , S. vol. 281 , 209 – 222 . New York : Plenum Press .
   Google Scholar
• Takahashi , T. , Kanda , T. , Imai , S. , Suzuki , T. , Kobayashi , I. and Murata , K. 1995 . Semotiadil inhibits the development of right ventricular hypertrophy and medial thickening of pulmonary arteries in a rat model of pulmonary hypertension . Cardiovasc. Drugs Ther. , 9 : 809 – 814 .
   PubMedGoogle Scholar
• Takahashi , T. , Kanda , T. , Imai , S. , Suzuki , T. , Kobayashi , I. and Murata , K. 1996 . Semotiadil improves survival of rats with monocrotaline‐induced pulmonary hypertension: Comparison with diltiazem . Eur. J. Pharmacol. , 295 (2‐3) : 226 – 234 .
   Google Scholar
• Takenaka , T. , Ogawa , Y. and Tobise , K. 1990 . Ca2+‐induced contraction and hyperreactivity of pulmonary arterial smooth muscle in monocrotaline‐treated rats . Jpn. Circ. J. , 54 : 515 – 523 .
   PubMedGoogle Scholar
• Tanaka , Y. , Schuster , D. P. , Davis , E. C. , Patterson , G. A. and Botney , M. D. 1996a . The role of vascular injury and hemodynamics in rat pulmonary artery remodeling . J. Clin. Invest. , 15 : 434 – 442 .
   Google Scholar
• Tanaka , Y. , Bernstein , M. L. , Mecham , R. P. , Patterson , G. A. , Cooper , J. D. and Botney , M. D. 1996b . Site‐specific responses to monocrotaline‐induced vascular injury: Evidence for two distinct mechanisms of remodeling . Am. J. Respir. Cell. Mol. Biol. , 145 : 390 – 397 .
   Google Scholar
• Tatebe , S. , Miyamura , H. , Sugawara , M. , Watanabe , H. and Eguchi , S. 1996 . Induction of right ventricular hypertrophy in neonatal guinea pigs by monocrotaline . Jpn. Circ. J. , 60 : 604 – 608 .
   PubMedGoogle Scholar
• Tateson , J. E. , Moneada , S. and Vane , J. R. 1977 . Effects of prostacyclin (PGX) on cyclic AMP concentrations in human platelets . Prostaglandins , 13 : 389 – 397 .
   PubMed Web of Science ®Google Scholar
• Taylor , D. W. , Wilson , D. W. , Lame , M. W. , Dunston , S. D. , Jones , A. D. and Segall , H. J. 1997 . Comparative cytotoxicity of monocrotaline and its metabolites in cultured pulmonary artery endothelial cells . Toxicol. Appl. Pharmacol. , 143 : 196 – 204 .
   PubMed Web of Science ®Google Scholar
• Thomas , E. F. 1934 . The toxicity of certain species of Crotalaria seed for the chicken, quail, turkey and dove . J. Am. Vet. Med. Assoc. , 85 : 617 – 622 .
   Google Scholar
• Thomas , H. C. , Lame , M. W. , Wilson , D. W. and Segall , H. J. 1996 . Cell cycle alterations associated with covalent binding of monocrotaline pyrrole to pulmonary artery endothelial cell DNA . Toxicol. Appl. Pharmacol. , 141 : 319 – 329 .
   PubMed Web of Science ®Google Scholar
• Thompson , A. R. and Harker , L. A. 1983 . Manual of hemostasis and thrombosis, , 3rd ed. , Philadelphia : F. A. Davis .
   Google Scholar
• Todorovich‐Hunter , L. , Johnson , D. J. , Ranger , P. , Keeley , F. W. and Rabinovitch , M. 1988 . Altered elastin and collagen synthesis associated with progressive pulmonary hypertension induced by monocrotaline: A biochemical and ultrastructural study . Lab. Invest. , 58 : 184 – 195 .
   PubMed Web of Science ®Google Scholar
• Todorovich‐Hunter , L. , Dodo , H. , Ye , C. , McCready , L. , Keeley , F. W. and Rabinovitch , M. 1992 . Increased pulmonary artery elastolytic activity in adult rats with monocrotaline‐induced progressive hypertensive pulmonary vascular disease compared with infant rats with nonprogressive disease . Am. Rev. Respir. Dis. , 146 : 213 – 223 .
   PubMed Web of Science ®Google Scholar
• Tomashefski , J. F. , Davies , P. , Boggis , C. , Greene , R. , Zapol , W. M. and Reid , L. M. 1983 . The pulmonary vascular lesions of the adult respiratory distress syndrome . Am. J. Pathol. , 112 : 112 – 126 .
   PubMed Web of Science ®Google Scholar
• Ts'ao , C. H. , Ward , W. F. and Port , C. D. 1983 . Radiation injury in rat lung. III . Radiat. Res. , 96 : 301 – 308 .
   PubMed Web of Science ®Google Scholar
• Tuchweber , B. , Kovacs , K. , Jago , M. V. and Beaulieu , T. 1974 . Effect of steroidal and nonsteroidal microsomal enzyme inducers on the hepatotoxicity of pyrrolizidine alkaloids in rats . Res. Commun. Chem. Pathol. Pharmacol. , 7 : 459 – 480 .
   PubMedGoogle Scholar
• Turner , J. H. and Lalich , J. J. 1965 . Experimental cor pulmonale in the rat . Arch. Pathol. , 79 : 409 – 418 .
   PubMedGoogle Scholar
• Umans , J. G. and Levi , R. 1995 . Nitric oxide in the regulation of blood flow and arterial pressure . Annu. Rev. Physiol. , 57 : 771 – 790 .
   PubMed Web of Science ®Google Scholar
• Valdivia , E. , Lalich , J. J. , Hayashi , Y. and Sonnad , J. 1967a . Alterations in pulmonary alveoli after a single injection of monocrotaline . Arch. Pathol. , 84 : 64 – 76 .
   PubMedGoogle Scholar
• Valdivia , E. , Sonnad , J. , Hayashi , Y. and Lalich , J. 1967b . Experimental interstitial pulmonary edema . Angiology , 18 : 378 – 383 .
   PubMed Web of Science ®Google Scholar
• Vallance , P. and Collier , J. 1994 . Biology and clinical relevance of nitric oxide . Br. Med. J. , 309 : 453 – 457 .
   PubMed Web of Science ®Google Scholar
• Van Camp , J. R. , Yian , C. and Lupinetti , F. M. 1994 . Regulation of pulmonary vascular resistance by endogenous and exogenous nitric oxide . Ann. Thorac. Surg. , 58 : 1025 – 1030 .
   PubMedGoogle Scholar
• Vincic , L. , Orr , F. W. , Warner , D. J. A , Suyama , K. L. and Kay , J. M. 1989 . Enhanced cancer metastasis after monocrotaline‐induced lung injury . Toxicol. Appl. Pharmacol. , 100 : 259 – 270 .
   PubMedGoogle Scholar
• Voelkel , N. F. 1997 . Drug‐induced pulmonary hypertension: Must history repeat itself? . Pulmonary Pharmacol. , 9 : 67 – 68 .
   Google Scholar
• Voelkel , N. and Reeves , J. T. 1979 . “ Primary pulmonary hypertension ” . In Pulmonary vascular diseases , Edited by: Moser , K. 573 – 628 . New York : Marcel Dekker .
   Google Scholar
• Voelkel , N. F. and Weir , E. K. 1989 . “ Etiologic mechanisms in pulmonary hypertension ” . In Lung biology in health and vascular disease. Pulmonary vascular physiology and pathophysiology , Edited by: Weir , E. K. and Reeves , J. T. vol. 38 , 513 – 539 . New York : Marcel Dekker .
   Google Scholar
• Voelkel , N. F. , Worthen , S. C. , Reeves , F. T. , Hensen , P. M. and Murphy , R. C. 1982 . Nonimmunological production of leukotrienes induced by platelet‐activating factor . Science , 218 : 286 – 288 .
   PubMed Web of Science ®Google Scholar
• Voelkel , N. F. , Tuder , R. M. , Bridges , J. and Arend , W. P. 1994 . lnterleukin‐1 receptor antagonist treatment reduces pulmonary hypertension generated in rats by monocrotaline . Am. J. Respir. Cell. Mol. Biol. , 11 : 664 – 675 .
   PubMed Web of Science ®Google Scholar
• Wagenvoort , C. A. 1980 . Lung biopsies in the differential diagnosis of thromboembolic versus primary pulmonary hypertension . Prog. Respir. Res. , 13 : 16 – 21 .
   Google Scholar
• Wagenvoort , C. A. and Wagenvoort , N. 1977 . Pathology of pulmonary hypertension , New York : John Wiley and Sons .
   Google Scholar
• Wagner , D. D. and Bonfanti , R. 1991 . Von Willebrand factor and the endothelium . Mayo Clin. Proc. , 66 : 621 – 627 .
   PubMedGoogle Scholar
• Walcott , G. , Burchell , H. B. and Brown , A. L. 1970 . Primary pulmonary hypertension . Am. J. Med. , 49 : 70 – 79 .
   PubMedGoogle Scholar
• Wanstall , J. C. and O'Donnell , S. R. 1990 . Endothelin and 5‐hydroxytryptamine on rat pulmonary artery in pulmonary hypertension . Eur. J. Pharmacol. , 6 : 159 – 160 .
   Google Scholar
• Watanabe , S. and Ogata , T. 1976 . Clinical and experimental study upon primary pulmonary hypertension . Jpn. Ciric. J. , 40 : 603 – 610 .
   PubMedGoogle Scholar
• Watson , S. P. , McConnell , R. T. and Lapetina , E. G. 1984 . The rapid formation of inositol phosphates in human platelets by thrombin is inhibited by prostacyclin . J. Biol. Chem. , 259 : 13199 – 13203 .
   PubMed Web of Science ®Google Scholar
• Werchan , P. M. , Gregory , T. J. , Summer , W. R. and McDonough , K. H. 1986 . In vitro right ventricular function in monocrotaline induced hypertrophy . Fed. Proc. , 45 : 776
   Google Scholar
• Werchan , P. M. , Summer , W. R. , Gerdes , A. M. and McDonough , K. H. 1989 . Right ventricular performance after monocrotaline‐induced pulmonary hypertension . Am. J. Physiol. , 256 : H1328 – H1335 .
   PubMed Web of Science ®Google Scholar
• White , S. M. and Roth , R. A. 1988 . Pulmonary platelet sequestration is increased following monocrotaline pyrrole treatment of rats . Toxicol. Appl. Pharmacol. , 96 : 465 – 475 .
   PubMedGoogle Scholar
• White , S. M. , Wagner , J. G. and Roth , R. A. 1989 . Effects of altered platelet number on pulmonary hypertension and platelet sequestration in monocrotaline pyrrole‐treated rats . Toxicol. Appl. Pharmacol. , 99 : 302 – 313 .
   PubMedGoogle Scholar
• Williams , W. J. 1983 . Hematology, , 3rd ed. , Edited by: Williams , W. J. , Beutler , E. , Erselv , A. J. and Lichtman , M. A. 1238 – 1255 . 1474 – 1488 . New York : McGraw‐Hill .
   Google Scholar
• Wilson , D. W. , Segall , H. J. , Pan , L. C. , Lame , M. W. , Estep , J. E. and Morin , D. 1992 . Mechanisms and pathology of monocrotaline pulmonary toxicity . Crit. Rev. Toxicol. , 22 : 307 – 325 .
   PubMed Web of Science ®Google Scholar
• Winter , C. K. and Segall , H. J. 1989 . “ Metabolism of pyrrolizidine alkaloids ” . In Toxicants of plant origin, vol. I, Alkaloids , Edited by: Cheeke , P. R. vol. I , 23 – 40 . Boca Raton, FL : CRC Press .
   Google Scholar
• Yan , C. C. and Huxtable , R. J. 1994 . Quantitation of the hepatic release of metabolites of the pyrrolizidine alkaloid, monocrotaline . Toxicol. Appl. Pharmacol. , 127 : 58 – 63 .
   PubMedGoogle Scholar
• Yan , C. C. and Huxtable , R. J. 1995a . The relationship between the concentration of the pyrrolizidine alkaloid monocrotaline and the pattern of metabolites released form the isolated liver . Toxicol. Appl. Pharmacol. , 130 : 1 – 8 .
   PubMed Web of Science ®Google Scholar
• Yan , C. C. and Huxtable , R. J. 1995b . Relationship between glutathione concentration and metabolism of the pyrrolizidine alkaloid, monocrotaline, in the isolated, perfused liver . Toxicol. Appl. Pharmacol. , 130 : 132 – 139 .
   PubMed Web of Science ®Google Scholar
• Yorikane , R. , Miyauchi , T. , Sakai , S. , Sakurai , T. , Yamaguchi , I. , Sugishita , Y. and Goto , K. 1993 . Altered expression of ETB‐receptor mRNA in the lung of rats with pulmonary hypertension . J. Cardiovasc. Pharmacol. , 22 (suppl 8) : S336 – S338 .
   PubMedGoogle Scholar
• Yuki , H. , Sato , S. , Arisaka , Y. , Kato , S. and Tomoike , H. 1994 . Orally administered beraprost sodium inhibits pulmonary hypertension induced by monocrotaline in rats. Tohoku J . Exp. Med. , 173 : 371 – 375 .
   Google Scholar
• Yuki , H. , Kato , S. , Saito , H. , Nakamura , H. and Tomoike , H. 1995 . Continuous inhibition of nitric oxide (NO) promotes pulmonary hypertension induced by monocrotaline in rats (abstr.) . Am. J. Respir. Crit. Care Med. , 151 : A729
   Google Scholar
• Zapol , W. M. and Jones , R. 1987 . Vascular components of ARDS . Am. Rev. Respir. Dis. , 136 : 471 – 474 .
   PubMed Web of Science ®Google Scholar
• Zapol , W. and Snider , M. 1977 . Pulmonary hypertension in severe acute respiratory failure . N. Engl. J. Med. , 296 : 476 – 480 .
   PubMed Web of Science ®Google Scholar
• Zhou , K. R. and Lai , Y. L. 1992 . α‐Difluoromethylornithine attenuates monocrotaline‐induced airway/lung dysfunction . J. Appl. Physiol. , 72 : 1914 – 1921 .
   PubMedGoogle Scholar