The Inflammatory Aspect of the Microcirculation in Hypertension: Oxidative Stress, Leukocytes/Endothelial Interaction, Apoptosis

REFERENCES

• Acevedo AD, Bowser SS, Gerritsen ME, Bizios R. (1993). Morphological and proliferative responses of endothelial cells to hydrostatic pressure: role of fibroblast growth factor. J Cell Physio 157:603–614.
   PubMed Web of Science ®Google Scholar
• Aoki K. (1963). Experimental studies on the rela-tionship between endocrine organs and hypertension in spontaneously hypertensive rats. I. Effects of hy-pophysectomy, adrenalectomy, thyroidectomy, ne-phrectomy and sympathectomy on blood pressure. Japan Heart J 4:443–461.
   PubMedGoogle Scholar
• Ardekani AM, Walker SJ, Donohue SJ, Stitzel RE, Connors ym, Vrana KE. (1989). Adrenocorticotro-pin and corticosterone levels in pre-weaning spon-taneously hypertensive rats. Life Science 44:919–925.
   Google Scholar
• Arndt H, Smith CW, Granger DN. (1993). Leuko-cyte-endothelial cell adhesion in spontaneously hy-pertensive and normotensive rats. Hypertension 21: 667–673.
   Google Scholar
• Auch-Schwelk W, Katusic ZS, Vanhoutte PM. (1992). Nitric oxide inactivates endothelium-derived contracting factor in the rat aorta. Hyper-tension 19:442–445.
   Google Scholar
• Babcock GT. (1999). How oxygen is activated and reduced in respiration. Proc Natl Acad Sci USA 96: 12971–12973.
   Google Scholar
• Babior BM. (1994). Activation of the respiratory burst oxidase. Environmental Health Perspectives 102(Suppl 10):53–56.
   Google Scholar
• Babior BM. (1999). NADPH oxidase: an update. Blood 93:1464–1476.
   PubMed Web of Science ®Google Scholar
• Babior BM, Curnutte JT, Kipnes RS. (1975). Bio-logical defense mechanisms. Evidence for the par-ticipation of superoxide in bacterial killing by xan-thine oxidase. J Lab Clin Med 85:235–244.
   Google Scholar
• Barroso-Aranda J, Schmid-Schönbein GW. (1989). Transformation of neutrophils as indicator of irre-versibility in hemorrhagic shock. Am J Physiol 257:H699–H852.
   Google Scholar
• Beckman JS, Beckman TW, Chen J, Marshall PM, Freeman BA. (1990). Apparent hydroxyl radical production from peroxynitrite: implications for en-dothelial injury by nitric oxide and superoxide. Proc Natl Acad Sci USA 87:1620–1624.
   PubMed Web of Science ®Google Scholar
• Beckman JS, Koppenol WH. (1996). Nitric oxide, superoxide, and peroxynitrite: the good, the bad, and ugly. Am J Physiol 271:C1424–C1437.
   PubMed Web of Science ®Google Scholar
• Berry C, Brosnan MJ, Fennell J, Hamilton CA, Do-miniczak AF. (2001). Oxidative stress and vascular damage in hypertension. Curr Opin Nephrol Hyper-tens 10:247–255.
   PubMed Web of Science ®Google Scholar
• Boegehold MA. (1993). Microvascular changes as-sociated with high salt intake and hypertension in Dahl rats. Int J Microcirculation: Clin Exp 12:143–156.
   Google Scholar
• Boegehold MA, Kotchen TA. (1990). Arteriolar net-work morphology in gracilis muscle of rats with salt-induced hypertension. Microvascular Res 40:169–178.
   Google Scholar
• Bohlen HG, Lobach D. (1978). In vivo study of mi-crovascular wall characteristics and resting control in young and mature spontaneously hypertensive rats. Blood Vessels 15:322–330.
   PubMedGoogle Scholar
• Buchanan TA, Sipos GF, Madrilejo N, Liu C, Carnpese VM. (1992). Hypertension without pe-ripheral insulin resistance in spontaneously hyper-tensive rats. Am J Physiol 262:E14–E19.
   Google Scholar
• Bursztyn M, Ben-Ishay D, Gutman A. (1992). Insu-lin resistance in spontaneously hypertensive rats but not in deoxycorticosterone-salt or renal vascular hy-pertension. J Hypertens 10:137–142.
   PubMedGoogle Scholar
• Cai H, Harrison DG. (2000). Endothelial dysfunc-tion in cardiovascular diseases: the role of oxidant stress. Circ Res 87:840–844.
   PubMed Web of Science ®Google Scholar
• Chan P, Liao SS, Hsu CT, Lee YS, Tomlinson B, Kuo JS, Cheng JT. (1999). Superoxide dismutase gene expression and activity in the brain of sponta-neously hypertensive rats and normotensive rats. Chin Med J (Engl) 112:1119–1124.
   PubMed Web of Science ®Google Scholar
• Chen TM, Prewitt RL, Dowell RF. (1981). Micro-vascular rarefaction in spontaneously hypertensive rat cremaster muscle. Am J Physiol 241:H306–H310.
   Google Scholar
• Clapham JC, Turner NC. (1997). Effects of the glu-cocorticoid II receptor antagonist mifepristone on hypertension in the obese Zucker rat. J Pharmacol Exp Ther 282:1503–1508.
   PubMed Web of Science ®Google Scholar
• deBlois D, Tea BS, Than VD, Tremblay J, Hamet P. (1997). Smooth muscle apoptosis during vascular regression in spontaneously hypertensive rats. Hy-pertension 29:340–349.
   Google Scholar
• DeLano FA, Schmid-Schönbein GW. (2001). Visu-alization of oxidative stress enzyme markers within a microvascular network. Proceedings of the 7th World Congress for Microcirculation pp. 3–45.
   Google Scholar
• Deng LY, Schiffrin EL. (1998). Endothelin-1 gene expression in blood vessels and kidney of spontane-ously hypertensive rats (SHR), L -NAME -treated SHR, and renovascular hypertensive rats. J Cardio-vasc Pharmacol 31(Suppl 1):S380–S383.
   Google Scholar
• Deveraux QL, Schendel SL, Reed JC. (2001). Anti-apoptotic proteins. The bc1-2 and inhibitor of apo-ptosis protein families. Cardiol Clin 19:57–74.
   Google Scholar
• Devlin AM, Clark JS, Reid JL, Dominiczak AF. (2000). DNA synthesis and apoptosis in smooth muscle cells from a model of genetic hypertension. Hypertension 36:110–115.
   Google Scholar
• Dickhout JG, Lee RM. (1999). Apoptosis in the muscular arteries from young spontaneously hyper-tensive rats. J Hypertens 17:1413–1419.
   Google Scholar
• Diez J, Fortulio MA, Zalba G, Etayo JC, Fortulio A, Ravassa S, Beaumont J. (1998). Altered regulation of smooth muscle cell proliferation and apoptosis in small arteries of spontaneously hypertensive rats. Eur Heart J 19(Suppl G):G29–G33.
   Google Scholar
• Diez J, Panizo A, Hernández M, Vega F, Sola I, For-tulio MA, Pardo J. (1997). Cardiomyocyte apoptosis and cardiac angiotensin-converting enzyme in spon-taneously hypertensive rats. Hypertension 30:1029–1034.
   PubMed Web of Science ®Google Scholar
• Dzielak DJ. (1992). The immune system and hyper-tension. Hypertension 19:136–144.
   Google Scholar
• Engelson ET, Schmid-Schönbein GW, Zweifach BW. (1986). The microvasculature in skeletal muscle. II. Arteriolar network anatomy in normo-tensive and spontaneously hypertensive rats. Micro-vasc Res 31:356–374.
   Google Scholar
• Fisslthaler B, Popp R, Kiss L, Potente M, Harder DR, Fleming I, Busse R. (1999). Cytochrome P450 2C is an EDHF synthase in coronary arteries. Na-ture 401:493–497.
   PubMed Web of Science ®Google Scholar
• Fleming I. (2001). Cytochrome p450 and vascular homeostasis. Circ Res 89:753–762.
   PubMed Web of Science ®Google Scholar
• Folkow B. (1990). Structural factor in primary and secondary hypertension. Hypertension 16:89–101.
   PubMed Web of Science ®Google Scholar
• Folkow B, Grirnby G, Thulesius O. (1958). Adaptive structural changes of the vascular walls in hyperten-sion and their relation to the control of the periph-eral resistance. Acta Physiol Scand 44:255–272.
   PubMedGoogle Scholar
• Fortufio MA, Zalba G, Ravassa S, D'Elom E, Beau-mont FJ, Fortulio A, Diez J. (1999). p53-mediated upregulation of BAX gene transcription is not in-volved in Bax-alpha protein overexpression in the left ventricle of spontaneously hypertensive rats. Hypertension 33:1348–1352.
   Google Scholar
• Friebe A, Miillershausen F, Smolenski A, Walter U, Schultz G, Koesling D. (1998). YC-1 potentiates ni-tric oxide- and carbon monoxide-induced cyclic GMP effects in human platelets. Mol Pharmacol 54: 962–967.
   PubMed Web of Science ®Google Scholar
• Gob e G, Browning J, Howard T, Hogg N, Winterford C, Cross R. (1997). Apoptosis occurs in endothelial cells during hypertension-induced microvascular rarefaction. J Structural Biol 118:63–72.
   Google Scholar
• Goda N, Suzuki K, Naito M, Takeoka S, Tsuchida E, Ishirnura Y, Tarnatani T, Suematsu M. (1998). Dis-tribution of heme oxygenase isoforms in rat liver: Topographic basis for carbon monoxide-mediated microvascular relaxation. J Clin Invest 101(4):604–612.
   Google Scholar
• Granger DN, Rutili G, McCord JM. (1981). Super-oxide radicals in feline intestinal ischemia. Gastro-enterology 81:22–29.
   PubMed Web of Science ®Google Scholar
• Greene AS. (1998). Life and death in the microcir-culation: a role for angiotensin II. Microcirculation 5:101–107.
   Google Scholar
• Griendling KK, Minieri CA, Ollerenshaw JD, Alex-ander RW. (1994). Angiotensin II stimulates NADH and NADPH oxidase activity in cultured vascular smooth muscle cells. Circ Res 74:1141–1148.
   PubMed Web of Science ®Google Scholar
• Griendling KK, Sorescu D, Lassegue B, Ushio-Fukai M. (2000). Modulation of protein kinase activity and gene expression by reactive oxygen species and their role in vascular physiology and pathophysiol-ogy. Arterioscler Thromb Vasc Biol 20:2175–2183.
   Google Scholar
• Griinfeld JP. (1990). Glucocorticoids in blood pres-sure regulation. Hormone Res 34:111–113.
   Google Scholar
• Gryglewski RJ, Palmer RMJ, Moncada S. (1986). Superoxide anion is involved in the breakdown of endothelium-derived vascular relaxing factor. Na-ture 320:454–456.
   PubMed Web of Science ®Google Scholar
• Harnet P. (1995). Proliferation and apoptosis of vascular smooth muscle in hypertension. Curr Opin Nephrol Hypertens 4:1–7.
   Google Scholar
• Harnet P, Richard L, Dam T-V, Teiger E, Orlov SN, Gaboury L, Gossard F, Tremblay J. (1995). Apo-ptosis in target organs of hypertension. Hyperten-sion 26:642–648.
   Google Scholar
• Harnet P, Thorin-Trescases N, Moreau P, Dumas P, Tea BS, deBlois D, Kren V, Pravenec M, Kunes J, Sun Y, Tremblay J. (2001). Workshop: excess growth and apoptosis: is hypertension a case of ac-celerated aging of cardiovascular cells? Hyperten-sion 37:760–766.
   Google Scholar
• Hansen-Smith FM, Morris LW, Greene AS, Lom-bard JH. (1996). Rapid microvessel rarefaction with elevated salt intake and reduced renal mass hyper-tension in rats. Circ Res 79:324–330.
   PubMed Web of Science ®Google Scholar
• Harper RN, Moore MA, Marr MC, Watts LE, Hutchins PM. (1978). Arteriolar rarefaction in the conjunctiva of human essential hypertension. Micro-vasc Res 16:369–372.
   PubMed Web of Science ®Google Scholar
• Hashimoto K, Makino S, Hirasawa R, Takao T, Sugawara M, Murakarni K. (1989). Abnormalities in the hypothalamo-pituitary-adrenal axis in spon-taneously hypertensive rats during development of hypertension. Endocrinology 125:1161–1167.
   PubMed Web of Science ®Google Scholar
• Hayashi S, Takarniya R, Makino N, Tarnatani T, Yamaguchi T, Tojo SJ, Ishirnura Y, Suematsu M. (1999). Induction of heme oxygenase-1 attenuates oxidative stress-induced leukocyte adhesion: Roles of bilirubin generated by the enzyme. Circ Res 85: 663–671.
   PubMed Web of Science ®Google Scholar
• Hayashi T, Tsurnura K, Suematsu C, Okada K, Fujii S, Endo G. (1999). Walking to work and the risk for hypertension in men: the Osaka Health Survey. Ann Intern Med 131:21–26.
   PubMed Web of Science ®Google Scholar
• Helrnke BP, Bremner SN, Zweifach BW, Skalak R, Schmid-Schönbein GW. (1997). Mechanisms for in-creased blood flow resistance due to leukocytes. Am J Physiol 273:H2884–H2890.
   Google Scholar
• Helrnke BP, Sugihara-Seki M, Skalak R, Schmid-Schönbein GW. (1998). A mechanism for erythro-cyte-mediated elevation of apparent viscosity by leukocytes in vivo without adhesion to the endothe-lium. Biorheology 35:437–448.
   Google Scholar
• Huang A, Koller A. (1996). Both nitric oxide and prostaglandin-mediated responses are impaired in skeletal muscle arterioles of hypertensive rats. J Hy-pertension 14:887–895.
   Google Scholar
• Hulrnan S, Fallmer B, Freyvogel N. (1993). Insulin resistance in the conscious spontaneously hyperten-sive rat: euglycemic hyperinsulinemic clamp study. Metabolism: Clin Exp 42:14–18.
   Google Scholar
• Hutchins PM, Darnell AE. (1974). Observations of a decreased number of small arterioles in spontane-ously hypertensive rats. Circ Res 34–35:161–165.
   Google Scholar
• Irnai T, Morita T, Shindo T, Nagai R, Yazaki Y, Kurihara H, Suematsu M, Katayarna S. (2001). Vascular smooth muscle cell-directed overexpres-sion of heme oxygenase-1 elevates blood pressure through attenuation of nitric oxide-induced vasodi-lation in mice. Circ Res 89:55–62.
   Google Scholar
• Ishizaka N, de Leon H, Laursen JIB, Fukui T, Wilcox JN, De Keulenaer G, Griendling KK, Alexander RW. (1997). Angiotensin II-induced hypertension in-creases heme oxygenase-1 expression in rat aorta. Circulation 96:1923–1929.
   PubMed Web of Science ®Google Scholar
• Ito H, Toni M, Suzuki T. (1995). Decreased super-oxide dismutase activity and increased superoxide anion production in cardiac hypertrophy of sponta-neously hypertensive rats. Clin Exp Hypertens 17: 803–816.
   PubMed Web of Science ®Google Scholar
• Jarasch ED, Bruder G, Heid HW. (1986). Signifi-cance of xanthine oxidase in capillary endothelial cells. Acta Physiol Scand Suppl 548:39–46.
   Google Scholar
• Jondal M, Xue Y, McConkey DJ, Okret S. (1995). Thymocyte apoptosis by glucocorticoids and cAMP. Curr Top Microbiol Immunol 200:67–79.
   PubMedGoogle Scholar
• Kanno K, Hirata Y, Irnai T, Iwashina M, Marurno F. (1994). Regulation of inducible nitric oxide syn-thase gene by interleukin-1 beta in rat vascular en-dothelial cells. Am J Physiol 267:H2318–H2324.
   PubMed Web of Science ®Google Scholar
• Khan AA, Soloski MJ, Sharp AH, Schilling G, Saba-tini DM, Li SH, Ross CA, Snyder SH. (1996). Lym-phocyte apoptosis: mediation by increased type 3 inositol 1,4,5-trisphosphate receptor. Science 273: 503–507.
   PubMed Web of Science ®Google Scholar
• Kharitonov VG, Sharma VS, Pilz RB, Magde D, Koesling D. (1995). Basis of guanylate cyclase acti-vation by carbon monoxide. Proc Natl Acad Sci USA 92:2568–2571.
   PubMedGoogle Scholar
• Khraibi AA. (1994). Irnrnunoregulatory failure in the pathophysiology of hypertension. News Physiol Sci 9:27–30.
   Google Scholar
• Khraibi AA, Norman RA, Dzielak DJ. (1984). Chronic irnrnunosuppression attenuates hyperten-sion in Okamoto spontaneous hypertensive rats. Am J Physiol 247:H722–H726.
   Google Scholar
• Kirnoto S, Nishida S, Funasaka K, Nakano T, Tera-moto K, Tomura TT. (1995). Regional distribution of superoxide dismutase in the brain and myocar- diurn of the stroke-prone spontaneously hyperten-sive rat. Clin Exp Pharmacol Physiol Suppl 1: S160–S161.
   Google Scholar
• Kimoto-Kinoshita S, Nishida S, Tomura TT. (1999). Age-related change of antioxidant capaci-ties in the cerebral cortex and hippocampus of stroke-prone spontaneously hypertensive rats. Neurosci Lett 273:41*#x2013;44.
   Google Scholar
• Koller A, Huang A. (1995). Shear stress-induced dilation is attenuated in skeletal muscle arterioles of hypertensive rats. Hypertension 25:758*#x2013;763.
   Google Scholar
• Komatsu S, Panes J, Russell JM, Anderson DC, Muzykantov VR, Miyasaka M, Granger DN. (1997). Effects of chronic arterial hypertension on constituconstitutive and induced intercellular adhesion molecule-1 expression in vivo. Hypertension 29:683*#x2013;689.
   Google Scholar
• Krishna G, Urda G, Tefera W, Lalwani ND, Theiss J. (1995). Simultaneous evaluation of dexamethasone-induced apoptosis and micronuclei in rat primary spleen cell cultures. Mutat Res 332:1*#x2013;8.
   Google Scholar
• Kroemer G, Reed JC. (2000). Mitochondrial control of cell death. Nat Med 6:513–519.
   PubMed Web of Science ®Google Scholar
• Kubes P, Suzuki M, Granger DN. (1991). Nitric oxide: an endogenous modulator of leukocyte adhesion. Proc Natl Acad Sci USA 88:4651*#x2013;4655.
   Google Scholar
• Kurose I, Wolf R, Cerwinka W, Granger DN. (1999). Microvascular responses to ischemia/reperfusion in normotensive and hypertensive rats. Hypertension 34:212*#x2013;216.
   Google Scholar
• Lacy F, Kailasarn MT, O'Connor DT, Schmid-Schönbein GW, Parmer RJ. (2000). Plasma hydro-gen peroxide production in human essential hyper-tension: role of heredity, gender, and ethnicity. Hy-
   Google Scholar
• Lacy F, O'Connor DT, Schmid-Schönbein GW. (1998). Plasma hydrogen peroxide production in
   Google Scholar
• Laine GA. (1988). Microvascular changes in the heart during chronic arterial hypertension. Circ Res
   Google Scholar
• Laine GA, Granger HJ. (1983). Permeability of in-testinal microvessels in chronic arterial hyperten-
   Google Scholar
• Landmesser U, Harrison DG. (2001). Oxidative stress and vascular damage in hypertension. Coron Artery Dis 12:455–461.
   PubMed Web of Science ®Google Scholar
• Lee J, Schmid-Sch*#x2013;nbein GW. (1995). Hemodynamic resistance, endothelial distensibility, and pseudopod formation. Ann Biomed Eng 23:226*#x2013;246.
   Google Scholar
• Levere RD, Martasek P, Escalante B, Schwartzman ML, Abraham NG. (1990). Effect of heme arginate administration on blood pressure in spontaneously hypertensive rats. J Clin Invest 86:213*#x2013;219.
   Google Scholar
• Lewis RM, Batchelor DC, Cockrem JF, Johnston BM, Bassett NS, Skinner SJ. (1998). Glucocorticoid activity in the fetal spontaneously hypertensive rat. Rep rod Fertil Dev 10:341–346.
   PubMedGoogle Scholar
• Li M, Fraser T, Wang J, Whitworth JA. (1997). Dexarnethasone-induced hypertension in the rat: ef-fects of L-arginine. Clin Exp Pharmacol Physiol 24: 730–732.
   PubMed Web of Science ®Google Scholar
• Lim HH, DeLano FA, Schmid-Schönbein GW. (2001). Life and cell death labeling in the microcir-culation of the spontaneously hypertensive rat. J Vasc Res 38:228–236.
   PubMedGoogle Scholar
• Liu JJ, Peng L, Bradley CJ, Zulli A, Shen J, Buxton BF. (2000). Increased apoptosis in the heart of ge-netic hypertension, associated with increased fibro-blasts. Cardiovasc Res 45:729–735.
   Google Scholar
• Lombard JH, Eskinder H, Kauser K, Osborn JL, Harder DL. (1990). Enhanced norepinephrine sen-sitivity in renal arteries at elevated transmural pres-sure. Am J Physiol 259:H29–H33.
   Google Scholar
• Lombard JH, Hess ME, Stekiel WJ. (1986). En-hanced response of SHR arterioles to oxygen during the development of hypertension. Am J Physiol 250: H761–H764.
   Google Scholar
• Lombard JH, Hess ME, Stekiel WJ. (1984). Neural and local control of arterioles in SHR. Hypertension 6:530–535.
   Google Scholar
• Lorant DE, Tophan MK, Whatley RE, McEver RP, McIntyre TM. (1993). Inflammatory roles of P-selectin. J Clin Invest 92:559–570.
   PubMed Web of Science ®Google Scholar
• Macho A, Hirsch T, Marzo I, Marchetti P, Dallaporta B, Susin SA, Zamzarni N, Kroemer G. (1997). Glu-tathione depletion is an early and calcium elevation is a late event of thyrnocyte apoptosis. J Immunol 158:4612–4619.
   PubMed Web of Science ®Google Scholar
• Matsuyama S, Reed JC. (2000). Mitochondria-dependent apoptosis and cellular pH regulation. Cell Death Differ 7:1155–1165.
   PubMed Web of Science ®Google Scholar
• Mayadas TN, Johnson RC, Rayburn H, Hynes RO, Wagner DD. (1993). Leukocyte rolling and extrav-asation are severely compromised in P-selectin de-ficient mice. Cell 74:541–554.
   Google Scholar
• McIntyre M, Bohr DF, Dominiczak AF. (1999). En-dothelial function in hypertension: the role of super-oxide anion. Hypertension 34:539–545.
   PubMed Web of Science ®Google Scholar
• Mondon CE, Reaven GM. (1988). Evidence of ab-normalities of insulin metabolism in rats with spon-taneous hypertension. Metabol Clin Exp 37:303–305.
   PubMed Web of Science ®Google Scholar
• Moreau P, Tea BS, Dam TV, Hamet P. (1997). Al-tered balance between cell replication and apoptosis in hearts and kidneys of newborn SHR. Hyperten-sion 30 (3pt2) : 720–724.
   Google Scholar
• Morita T, Mitsialis SA, Kioke H, Liu Y, Kouremba-nas S. (1997). Carbon monoxide controls the pro-liferation of hypoxic vascular smooth muscle cells. J Biol Chem 272:32804–32809.
   PubMed Web of Science ®Google Scholar
• Morita T, Perrella MA, Lee ME, Kourembanas S. (1995). Smooth muscle cell-derived carbon monox- ide is a regulator of vascular cGMP. Proc Natl Acad Sci USA 92:1475–1479.
   PubMed Web of Science ®Google Scholar
• Morris DJ, Gorsline J, Tresco PA, Harnik M. (1985). The effects of 19-nor-aldosterone on blood pressure of adrenalectomized spontaneously hypertensive rats. Steroids 46:1003–1010.
   Google Scholar
• Motterlini R, Gonzales A, Foresti R, Clark JE, Green CJ, Winslow RM. (1998). Heme oxygenase-1-derived carbon monoxide contributes to the sup-pression of acute hypertensive responses in vivo. Circ Res 83:568–577.
   PubMed Web of Science ®Google Scholar
• Mulvany MJ, Aalkjaer C. (1990). Structure and function of small arteries. Physiol Rev 70:921–962.
   PubMed Web of Science ®Google Scholar
• Nakazono K, Watanabe N, Matsuno K, Sasaki J, Sato T, Inoue M. (1991). Does superoxide underlie the pathogenesis of hypertension? Proc Natl Acad Sci USA 88:10045–10048.
   PubMed Web of Science ®Google Scholar
• Node K, Huo Y, Ruan X, Yang B, Spiecker M, Ley K, Zeldin DC, Liao JK. (1999). Anti-inflammatory properties of cytochrome P450 epoxygenase-derived eicosanoids. Science 285:1276–1279.
   PubMed Web of Science ®Google Scholar
• Nora EH, Munzenrnaier DH, Hansen-Smith FM, Lombard JH, Greene AS. (1998). Localization of the ANG II type 2 receptor in the microcirculation of skeletal muscle. Am J Physiol 275:H1395–H1403.
   Google Scholar
• Nora EH, Tonellato PJ, Greene AS. (2000). Quan-tification of the contribution of type 1 and type 2 angiotensin II receptors to the net tissue specific ef-fect of angiotensin II. Ann Biomed Eng 28:653–664.
   Google Scholar
• Nyhof RA, Laine GA, Meininger GA, Granger HJ. (1983). Splanchnic circulation in hypertension. Fed Proc 42:1690–1693.
   Google Scholar
• Ohrnori M, Kitoh Y, Harada K, Sugimoto K, Fu-jimura A. (2000). Polymorphonuclear leukocytes (P1VENs) functions in SHR, L-NAME- and DOCA/ salt-induced hypertensive rats. J Hypertens 18:703–707.
   Google Scholar
• Parks DA, Bulldey GB, Granger DN, Hamilton SR, McCord JM. (1982). Ischemic injury in the cat small intestine: role of superoxide radicals. Gastroenterol-ogy 82:9–15.
   PubMed Web of Science ®Google Scholar
• Parks DA, Granger DN. (1986). Xanthine oxidase: biochemistry, distribution and physiology. Acta Physiol Scand Suppl 548:87–99.
   PubMedGoogle Scholar
• Pfeffer KB, Huecksteadt TP, Hoidal JR. (1994). Xanthine dehydrogenase and xanthine oxidase ac-tivity and gene expression in renal epithelial cells. J Immunol 153:1789–1797.
   PubMedGoogle Scholar
• Planey SL, Litwack G. (2000). Glucocorticoid-induced apoptosis in lymphocytes. Biochem Biophys Res Commun 279:307–312.
   PubMed Web of Science ®Google Scholar
• Prewitt RL, Chen TM, Dowell RF. (1982). Develop-ment of microvascular rarefaction in the spontane-ously hypertensive rat. Am J Physiol 243:H243–H251.
   Google Scholar
• Price RJ, Skalak TC. (1998). Distribution of cellular proliferation in skeletal muscle transverse arterioles during maturation. Microcirculation 5:39–47.
   Google Scholar
• Provencher PH, Saltis J, Funder JW. (1995). Glu-cocorticoids but not mineralocorticoids modulate endothelin-1 and angiotensin II binding in SHR vas-cular smooth muscle cells. J Steroid Biochem Mol Biol 52:219–225.
   Google Scholar
• Qiu C, and Baylis C. (2000). Dexarnethasone wors-ens nitric oxide inhibition-induced hypertension and renal dysfunction. Am J Hypertens 13:1097–1102.
   Google Scholar
• Rajagopalan S, Kurz S, Miinzel T, Tarpey M, Free-man BA, Griendling KK. (1996). Angiotensin II-mediated hypertension in the rat increases vascular superoxide production via membrane NADH/NADPH oxidase activation. Contribution to alterations of va-somotor tone. J Clin Invest 97:1916–1923.
   Google Scholar
• Rajashree S, Puvanakrishnan R. (1998). Dexarneth-asone induced alterations in enzymatic and nonen-zymatic antioxidant status in heart and kidney of rats. Mol Cell Biochem 181:77–85.
   PubMed Web of Science ®Google Scholar
• Reed JC, Kroemer G. (2000). Mechanisms of mito-chondrial membrane permeabilization. Cell Death Dffer 7:1145.
   PubMed Web of Science ®Google Scholar
• Reed JC, Miyashita T, Takayarna S. (1996). Bc1-2 family proteins: regulators of cell death involved in the pathogenesis of cancer and resistance to therapy. J Cell Biochem 60:23–32.
   PubMed Web of Science ®Google Scholar
• Rizzoni D, Rodella L, Porteri E, Rezzani R, Guelfi D, Piccoli A, Castellano M, Muiesan ML, Bianchi R, Rosei EA. (2000). Time course of apoptosis in small resistance arteries of spontaneously hypertensive rats. J Hypertens 18:885–891.
   Google Scholar
• Rocha R, Chander PN, Zuckerman A, Stier CT Jr. (1999). Role of aldosterone in renal vascular injury in stroke-prone hypertensive rats. Hypertension 33: 232–237.
   PubMed Web of Science ®Google Scholar
• Roman RJ. (2002). P-450 metabolites of arachi-donic acid in the control of cardiovascular function. Physiol Rev 82:131–185.
   PubMedGoogle Scholar
• Ruch W, Baumann JIB, Hausler A, Often UH, Siegl H, Girard J. (1984). Importance of the adrenal cor-tex for development and maintenance of hyperten-sion in spontaneously hypertensive rats. Acta Endo-crinol (Copenh) 105:417–424.
   PubMedGoogle Scholar
• Sacerdoti D, Escalante B, Abraham NG, McGiff JC, Levere RD. (1989). Treatment with tin prevents the development of hypertension in spontaneously hy-pertensive rats. Science 243:388–390.
   PubMed Web of Science ®Google Scholar
• Saruta T. (1996). Mechanism of glucocorticoid-induced hypertension. Hypertens Res 19:1–8.
   PubMedGoogle Scholar
• Sato A, Suzuki H, Nakazato Y, Shibata H, Inagarni T, Saruta T. (1994). Increased expression of vascu-lar angiotensin II type 1A receptor gene in glucocor-ticoid-induced hypertension. J Hypertens 12:511–516.
   Google Scholar
• Schirnrner BP, Parker KL. (1996). Adrenocortico-tropic hormone; adrenocortical steroids and their synthetic analogs; inhibitors of the synthesis and ac-tions of adrenocortical hormones. In: Hardman JG, Lirnbird LE, Molinoff PB, Ruddon RW, Gilman AG, editors. Goodman and Gilman 's The Pharmacologi-cal Basis of Therapeutics. New York: McGraw-Hill, pp. 1459–1485.
   Google Scholar
• Schmid-Schönbein GW, Seiffge D, DeLano FA, Shen K, Zweifach BW. (1991). Leukocyte counts and activation in spontaneously hypertensive and normotensive rats. Hypertension 17:323–330.
   PubMed Web of Science ®Google Scholar
• Schmid-Schönbein GW, Zweifach BW, DeLano FA, Chen P. (1987). Microvascular tone in a skeletal muscle of spontaneously hypertensive rats. Hyper-tension 9:164–171.
   Google Scholar
• Schnackenberg CG, Welch WJ, Wilcox CS. (1998). Normalization of blood pressure and renal vascular resistance in SHR with a membrane-permeable su-peroxide dismutase mimetic: role of nitric oxide. Hypertension 32:59–64.
   PubMed Web of Science ®Google Scholar
• Schwartz EA, Bizios R, Medow MS, Gerritsen ME. (1999). Exposure of human vascular endothelial cells to sustained hydrostatic pressure stimulates proliferation. Involvement of the alphaV integrins. Circ Res 84:315–322.
   PubMed Web of Science ®Google Scholar
• Semafuko WE, Morris DJ. (1991). Effect of high calcium diet on the development of high blood pres-sure in intact spontaneously hypertensive rats and in adrenalectomized spontaneously hypertensive rats treated with aldosterone. Steroids 56:131–135.
   Google Scholar
• Sessa WC, Abraham NG, Escalante B, Schwartzman ML. (1989). Manipulation of cytochrome P450-dependent renal thromboxane synthase activity in spontaneously hypertensive rats. J Hypertens 7: 37–42.
   Google Scholar
• Shah J, Jandhyala BS. (1995). Age-dependent alter-ations in Na+, K(+)-ATPase activity in the central nervous system of spontaneously hypertensive rats: relationship to the development of high blood pres-sure. Clin Exp Hypertens 17:751–767.
   PubMed Web of Science ®Google Scholar
• Shen K, DeLano FA, Zweifach BW, Schmid-S chönb ein GW. ( 1995 ) . Circulating leukocyte counts, activation, and degranulation in Dahl hyper-tensive rats. Circ Res 76:276–283.
   PubMed Web of Science ®Google Scholar
• Shen K, Sung KL, Whittemore BE, DeLano FA, Zweifach BW, Schmid- Schönbein GW. (1995 ) . Properties of circulating leukocytes in spontaneously hypertensive rats. Biochem Cell Biol 73:491–500.
   PubMed Web of Science ®Google Scholar
• Shichijo K, Ito M, Sekine I. (1991). The mechanism of low susceptibility to stress in gastric lesions of spontaneously hypertensive rats. Life Sci 49:2023–2029.
   Google Scholar
• Shikura S, Naito S, Chaoyien H, Shichijo K, Kawase Y, Ito M, Sekine I, Irnarnura K. (1989). The role of the sympathetic nervous system in cysteamine-induced gastric lesions in rats. Scand J Gastroen-terol 162:206–209.
   Google Scholar
• Sholter BE, Armstrong PW. (2000). Adverse effects of corticosteroids on the cardiovascular system. Can J Cardiol 16:505–511.
   PubMed Web of Science ®Google Scholar
• Skalak TC, Price RJ, Zeller PJ. (1998). Where do new arterioles come from? Mechanical forces and microvessel adaptation. Microcirculation 5:91–94.
   Google Scholar
• Skalak TC, Schmid-Schönbein GW. (1986). The microvasculature in skeletal muscle. W. A model of the capillary network. Microvasc Res 32:333–347.
   PubMedGoogle Scholar
• Suematsu M, DeLano FA, Poole DC, Engler RL, Miyasaka M, Zweifach BW, Schmid-Schönbein GW. (1994). Spatial and temporal correlation between leukocyte behavior and cell injury in postischemic rat skeletal muscle microcirculation. Lab Invest 70: 684–695.
   PubMedGoogle Scholar
• Suematsu M, Goda N, Sano T, Kashiwagi S, Shinoda Y, Ishirnura Y. (1995). Carbon monoxide: An en-dogenous modulator of sinusoidal tone in the per-fused rat liver. J Clin Invest 96:2431–2437.
   PubMed Web of Science ®Google Scholar
• Suematsu M, Ishirnura Y. (2000). The heme oxy-genase-carbon monoxide system: A regulator of hepatobiliary function. Hepatology 31:3–6.
   PubMed Web of Science ®Google Scholar
• Suematsu M, Suzuki H, Tamatani T, Iigou Y, DeLano FA, Miyasaka M, Forrest MJ, Kannagi R, Zweifach BW, Ishirnura Y, Schmid-Schönbein GW. (1995). Impairment of selectin-mediated leukocyte adhesion to venular endothelium in spontaneously hypertensive rats. J Clin Invest 96:2009–2016.
   Google Scholar
• Sun X-M, Dinsdale D, Snowden RT, Cohen GM, Skilleter DN. (1992). Characterization of apoptosis in thymocytes isolated from dexarnethasone-treated rats. Biochem Pharmacol 44:2131–2137.
   PubMed Web of Science ®Google Scholar
• Sutton DW, Schmid-Schönbein GW. (1992). Eleva-tion of organ resistance due to leukocyte perfusion. Am J Physiol 262:H1646–H1650.
   Google Scholar
• Suzuki H, DeLano FA, Jarnshidi N, Katz D, Mori M, Kosaki K, Gottlieb RA, Ishii H, Schmid-Schönbein GW. (1999). Enhanced DNA fragmentation in the thymus of spontaneously hypertensive rats. Am J Physiol 276:H2135–H2140.
   Google Scholar
• Suzuki H, DeLano FA, Parks DA, Jarnshidi N, Granger DN, Ishii H, Suematsu M, Zweifach BW, Schmid-Schönbein GW. (1998). Xanthine oxidase activity associated with arterial blood pressure in spontaneously hypertensive rats. Proc Natl Acad Sci USA 95:4754–4759.
   PubMed Web of Science ®Google Scholar
• Suzuki H, Miura S, Mori M, Akiba Y, Nagahashi S, Zweifach BW, Ishii H, Schmid-Schönbein GW. (1999). Protective role of adrenal glucocorticoids for gastric mucosa in spontaneously hypertensive rats. J Gastroenterol Hepatol 14:364–371.
   Google Scholar
• Suzuki H, Poole DC, Zweifach BW, Schmid-Schönbein GW. (1995). Temporal correlation be-tween maximum tetanic force and cell death in post-ischemic rat skeletal muscle. J Clin Invest 96:2892–2897.
   Google Scholar
• Suzuki H, Schmid-Schönbein GW, Suematsu M, DeLano FA, Forrest MJ, Miyasaka M, Zweifach BW. (1994). Impaired leukocyte-endothelial cell interac-tion in spontaneously hypertensive rats. Hyperten-sion 24:719–727.
   PubMed Web of Science ®Google Scholar
• Suzuki H, Suematsu M, Schrnid-Schönbein GW. (1999). Microvascular oxidative stress, immune re-action and apoptosis in hypertensives. Clin Hemorheol Microcirc 21:161–168.
   Google Scholar
• Suzuki H, Swei A, Zweifach BW, Schmid-Schönbein GW. (1995). In vivo evidence for microvascular oxi-dative stress in spontaneously hypertensive rats - Hydroethidine microfluorography. Hypertension 25:1083–1089.
   PubMed Web of Science ®Google Scholar
• Suzuki H, Zweifach BW, Forrest MJ, Schmid-Schönbein GW. (1995). Modification of leukocyte adhesion in spontaneously hypertensive rats by adrenal corticosteroids. J Leukoc Biol 57:20–26.
   Google Scholar
• Suzuki H, Zweifach BW, Schmid-Schönbein GW. (1995). Dependance of elevated mesenteric arterio-lar tone on glucocorticoids in spontaneously hyper-tensive rats. Int J Microcirc 15:309–315.
   Google Scholar
• Suzuki H, Zweifach BW, Schmid-Schönbein GW. (1996). Glucocorticoid modulates vasodilator re-sponse of mesenteric arterioles in spontaneously hy-pertensive rats. Hypertension 27:114–118.
   Google Scholar
• Suzuki H, Zweifach BW, Schmid-Schönbein GW. (1997). The multifaceted contribution of microvas-cular abnormalities to the pathophysiology of the hypertensive syndrome. In: Zanchetti A, Mancia G, editors. Handbook of Hypertension Vol. 17, Patho-physiology of Hypertension. Amsterdam: Elsevier Science, pp. 482–523.
   Google Scholar
• Suzuki H, Zweifach BW, Schmid-Schönbein GW. (1995). Vasodilator response of mesenteric arteri-oles to histamine in spontaneously hypertensive rats. Hypertension 26:397–400.
   PubMed Web of Science ®Google Scholar
• Swei A, Lacy F, Delano FA, Parks DA, Schmid-Schönbein GW. (1999). A mechanism of oxygen free radical production in the Dahl hypertensive rat. Microcirculation 6:179–187.
   PubMed Web of Science ®Google Scholar
• Swei A, Lacy F, DeLano FA, Schmid-Schönbein GW. (1997). Oxidative stress in the Dahl hyperten-sive rat. Hypertension 30:1628–1633.
   PubMed Web of Science ®Google Scholar
• Takeichi N, Ba D, Kobayashi H. (1981). Natural cytotoxic autoantibody against thymocytes in spon-taneously hypertensive rats. Cell Immunol 60:181–190.
   PubMed Web of Science ®Google Scholar
• Takeichi N, Ba D, Suzuki K, Kobayashi H. (1985). The arrest of T cell maturation in spontaneously hypertensive rats with a deficient production of thy-mic factors. Acta Pathol Jpn 35:351–360.
   PubMedGoogle Scholar
• Takeichi N, Hamada J, Takirnoto M, Fujiwara K, Kobayashi H. (1988). Depression of T cell-mediated immunity and enhancement of autoantibody pro-duction by natural infection with microorganisms in spontaneously hypertensive rats (SHR). Microbiol Immunol 32:1235–1244.
   PubMed Web of Science ®Google Scholar
• Takeichi N, Suzuki K, Okayasu H, Kobayashi H. ( 1980 ) . Immunological depression in spontane-ously hypertensive rats. Clin Exp Immunol 40:120–126.
   PubMed Web of Science ®Google Scholar
• Thompson TN, La Celle PL, Cokelet GR. (1989). Perturbation of red blood cell flow in small tubes by white blood cells. Pflugers Arch 413:372–377.
   Google Scholar
• Tokoro T, Ito H, Suzuki T. (1996). Alterations in mitochondrial DNA and enzyme activities in hyper-trophied myocardium of stroke-prone SHRS. Clin Exp Hypertens 18:595–606.
   PubMed Web of Science ®Google Scholar
• Touyz RM. (2000). Oxidative stress and vascular damage in hypertension. Curr Hypertens Rep 2:98–105.
   PubMedGoogle Scholar
• Tsai AG, Friesenecker B, Mazzoni MC, Kerger H, Buerk DG, Johnson PC, Intaglietta M. (1998). Mi-crovascular and tissue oxygen gradients in the rat mesentery. Proc Natl Acad Sci USA 95:6590–6595.
   PubMed Web of Science ®Google Scholar
• Ushio-Fukai M, Alexander RW, Akers M, Griendling KK. (1998). p38 Mitogen-activated protein kinase is a critical component of the redox-sensitive signaling pathways activated by angiotensin II. Role in vas-cular smooth muscle cell hypertrophy. J Biol Chem 273:15022–15029.
   Google Scholar
• Valentine JF, Nick HS. (1994). Glucocorticoids re-press basal and stimulated manganese superoxide dismutase levels in rat intestinal epithelial cells. Gastroenterology 107:1662–1670.
   PubMedGoogle Scholar
• Vogt CJ, Schmid-Schönbein GW. (2001). Microvas-cular endothelial cell death and rarefaction in the glucocorticoid-induced hypertensive rat. Microcir-culation 8:129–139.
   PubMedGoogle Scholar
• Wakabayashi Y, Takamiya R, Mizuki A, Kyokane T, Goda N, Yamaguchi T, Takeoka S, Tsuchida E, Suematsu M, Ishirnura Y. (1999). Carbon monoxide overproduced by heme oxygenase-1 causes a reduc-tion of vascular resistance in perfused rat liver. Am J Physio 277:G1088–G1096.
   Google Scholar
• Walker BR, Best R, Shackleton CH, Padfield PL, Edwards CR. (1996). Increased vasoconstrictor sen-sitivity to glucocorticoids in essential hypertension. Hypertension 27:190–196.
   PubMed Web of Science ®Google Scholar
• Walker BR, Phillips DI, Noon JP, Panarelli M, An-drew R, Edwards HV, Holton DW, Seckl JR, Webb DJ, Watt GC. (1998). Increased glucocorticoid activity in men with cardiovascular risk factors. Hypertension 31:891–895.
   PubMed Web of Science ®Google Scholar
• Wadington CO, Kramer LB, Schuetz EG, Zilai J, Grogan W1VI, Guzelian P, Gizek F, Schoolwerth AC. (1992). Corticosterone 6 beta-hydroxylation corre-lates with blood pressure in spontaneously hyper-tensive rats. Am J Physiol 262:F927–F931.
   Google Scholar
• Watt GC, Harrap SB, Foy CJ, Holton DW, Edwards Fly, Davidson HR, Connor ym, Lever AF, Fraser R. (1992). Abnormalities of glucocorticoid metabolism and the renin-angiotensin system: a four-corners ap-proach to the identification of genetic determinants of blood pressure. J Hypertens 10:473–482.
   PubMed Web of Science ®Google Scholar
• Weiss SJ. (1989). Tissue destruction by neutrophils. N Engl J Med 320:365–376.
   PubMed Web of Science ®Google Scholar
• Wennberg E, Hagberg H, Haljarnae H. (1984). The response of the awake spontaneously hypertensive rats to acute blood loss. Acta Anesth Scand 28:457–461.
   Google Scholar
• Wexler BC. (1980). Transplantation of pituitary and adrenal glands of spontaneously hypertensive rats into hypophysectomized or adrenalectomized, normotensive Sprague-Dawley rats. Br J Exp Pathol 61:429–439.
   Google Scholar
• Winrow VR, Winyard PG, Morris CJ, Blake DR. (1993). Free radicals in inflammation: second mes-sengers and mediators of tissue destruction. Br Med Bull 49:506–522.
   PubMed Web of Science ®Google Scholar
• Wu CH, Chi JC, Jerng JS, Lin SJ, Jan KM, Wang DL, Chien S. (1990). Transendothelial macromolecular transport in the aorta of spontaneously hypertensive rats. Hypertension 16:154–161.
   Google Scholar
• Wu R, Millette E, Wu L, de Champlain J. (2001). Enhanced superoxide anion formation in vascular tissues from spontaneously hypertensive and des-oxycorticosterone acetate-salt hypertensive rats. J Hypertens 19:741–748.
   PubMed Web of Science ®Google Scholar
• Wyllie AH. (1980). Glucocorticoid-induced thymo-cyte apoptosis is associated endogenous endonucle-ase activation. Nature 284:555–556.
   PubMed Web of Science ®Google Scholar
• Wyllie AH, Kerr JF, Currie AR. (1980). Cell death: the significance of apoptosis. Int Rev Cytol 68:251–306.
   PubMedGoogle Scholar
• Ying WZ, Sanders PW. (2001). Cytochrome c me-diates apoptosis in hypertensive nephrosclerosis in Dahl/Rapp rats. Kidney Int 59:662–672.
   Google Scholar
• Yuan YV, Kitts DD, Godin DV. (1996). Heart and red blood cell antioxidant status and plasma lipid levels in the spontaneously hypertensive and normo- tensive Wistar-Kyoto rat. Can J Physiol Pharmacol 74:290–297.
   Google Scholar
• Zafari AM, Ushio-Fukai M, Akers M, Yin Q, Shah A, Harrison DG, Taylor WR, Griendling KK. (1998). Role of NADH/NADPH oxidase-derived H202 in an-giotensin II-induced vascular hypertrophy. Hyper-tension 32:488–495.
   Google Scholar
• Zalba G, Beaumont FJ, San Jose G, Fortuno A, For-tuno MA, Etayo JC, Diez J. (2000). Vascular NADH/NADPH oxidase is involved in enhanced su-peroxide production in spontaneously hypertensive rats. Hypertension 35:1055–1061.
   PubMed Web of Science ®Google Scholar
• Zalba G, San Jose G, Moreno MU, Fortuno MA, For-tuno A, Beaumont FJ, Diez J. (2001). Oxidative stress in arterial hypertension: role of NAD(P)H oxi-dase. Hypertension 38:1395–1399.
   PubMed Web of Science ®Google Scholar
• Zamzami N, Marchetti P, Castedo M, Decaudin D, Macho A, Hirsch T, Susin SA, Petit PX, Mignotte B, Kroemer G. (1995). Sequential reduction of mito-chondrial transmembrane potential and generation of reactive oxygen species in early programmed cell death. J Exp Med 182:367–377.
   PubMed Web of Science ®Google Scholar
• Zeller PJ, Skalak TC, Ponce AM, Price RJ. (2001). In vivo chemotactic properties and spatial expres-sion of PDGF in developing mesenteric microvascu-lar networks. Am J Physiol Heart Circ Physiol 280: H2116–H2125.
   Google Scholar
• Zhao Z, Francis CE, Welch G, Loscalzo J, Ravid K. (1997). Reduced glutathione prevents nitric oxide-induced apoptosis in vascular smooth muscle cells. Biochim Biophys Acta 1359:143–252.
   PubMed Web of Science ®Google Scholar