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Review

Vasoactive peptides in cardiovascular (patho)physiology

, , , &
Pages 531-552 | Published online: 10 Jan 2014

References

  • Ferrario CM, Strawn WB. Role of the renin–angiotensin–aldosterone system and proinflammatory mediators in cardiovascular disease. Am. J. Cardiol.98(1), 121–128 (2006).
  • Mehta PK, Griendling KK. Angiotensin II cell signaling: physiological and pathological effects in the cardiovascular system. Am. J. Physiol. Cell Physiol.292(1), C82–C97 (2007).
  • Touyz RM. Molecular and cellular mechanisms in vascular injury in hypertension: role of angiotensin. Curr. Opin. Nephrol. Hypertens.14(2), 125–131 (2005).
  • Yanagisawa M, Kurihara H, Kimura S et al. A novel potent vasoconstrictor peptide produced by vascular endothelial cells. Nature332, 411–415 (1988).
  • Kishi F, Minami K, Okishima N et al. Novel 31-amino acid-length endothelins cause constriction of vascular smooth muscle. Biochem. Biophys. Res. Commun.248, 387–390 (1998).
  • Ducancel F. Endothelin-like peptides. Cell Mol. Life Sci.62(23), 2828–2839 (2005).
  • Maguire JJ, Davenport AP. Is urotensin-II the new endothelin? Br. J. Pharmacol.137, 579–588 (2002).
  • Haynes WG, Webb DJ. Contribution of endogenous generation of endothelin-1 to basal vascular tone. Lancet344, 852–854 (1994).
  • Russell FD, Skepper JN, Davenport AP. Human endothelial cell storage granules: a novel intracellular site for isoforms of the endothelin converting enzyme. Circ. Res.83, 314–321 (1998).
  • Sessa WC, Kaw S, Hecker M, Vane JR. The biosynthesis of endothelin-1 by human polymorphonuclear leukocytes. Biochem. Biophys. Res. Commun.174, 613–618 (1991).
  • Fukunaga M, Fujiwara Y, Ochi S et al. Stimulatory effect of thrombin on endothelin-1 production in isolated glomeruli and cultured mesangial cells of rats. J. Cardiovasc. Pharmacol.17, S411–S413 (1991).
  • Tirapelli CR, Fecteau MH, Honore JC, Legros E, Gobeil F, D’Orleans-Juste P. Enzymatic pathways involved in the generation of endothelin-1(1–31) from exogenous big endothelin-1 in the rabbit aorta. Br. J. Pharmacol.148(4), 527–535 (2006).
  • Xu D, Emoto N, Giaid A et al. ECE-1: a membrane-bound metalloprotease that catalyzes the proteolytic activation of big endothelin-1. Cell78, 473–485 (1994).
  • Emoto N, Yanagisawa M. Endothelin-converting enzyme-2 is a membrane-bound, phosphoramidon-sensitive metalloprotease with acidic pH optimum. J. Biol. Chem.270, 15262–15268 (1995).
  • Yanagisawa H, Hammer RE, Richardson JA et al. Disruption of ECE-1 and ECE-2 reveals a role for endothelin-converting enzyme-2 in murine cardiac development. J. Clin. Invest.105, 1373–1382 (2000).
  • Davenport AP. International Union of Pharmacology. XXIX. Update on endothelin receptor nomenclature. Pharmacol. Rev.54, 219–226 (2002).
  • Karne S, Jayawickreme CK, Lerner MR. Cloning and characterization of an endothelin-3 specific receptor (ETC receptor) from Xenopus laevis dermal melanophores. J. Biol. Chem.268, 19126–19133 (1993).
  • Cannan CR, Burnett JC, Lerman A. Enhanced coronary vasoconstriction to endothelin-B-receptor activation in experimental congestive heart failure. Circulation93, 646–651 (1996).
  • Deng LY, Li JS, Schiffrin EL. Activation of endothelin ETA receptors masks the constrictor role of endothelin ETB receptors in rat isolated small mesenteric arteries. Br. J. Pharmacol.120(7), 1376–1382 (1997).
  • Haynes WG, Strachan FE, Webb DJ. Endothelin ETA and ETB receptors cause vasoconstriction of human resistance and capacitance vessels in vivo. Circulation92, 357–363 (1995).
  • Deng LY, Li JS, Schiffrin EL. Endothelin receptor subtypes in resistance arteries from humans and rats. Cardiovasc. Res.29(4), 532–535 (1995).
  • Schiffrin EL, Touyz RM. Vascular biology of endothelin. J. Cardiovasc. Pharmacol.32(Suppl. 3), S2–S13 (1998).
  • Sugden PH. An overview of endothelin signaling in the cardiac myocyte. J. Mol. Cell Cardiol.35(8), 871–886 (2003).
  • Douglas SA, Ohlstein EH. Signal transduction mechanisms mediating the vascular actions of endothelin. J. Vasc. Res.34(3), 152–164 (1997).
  • Marasciulo FL, Montagnani M, Potenza MA. Endothelin-1: the yin and yang on vascular function. Curr. Med. Chem.13(14), 1655–1665 (2006).
  • Miao L, Dai Y, Zhang J. Mechanism of RhoA/Rho kinase activation in endothelin-1- induced contraction in rabbit basilar artery. Am. J. Physiol.283, H983–H989 (2002).
  • Fellner SK, Arendshorst W. Endothelin-A and -B receptors, superoxide, and Ca2+ signaling in afferent arterioles. Am. J. Physiol. Renal Physiol.292(1), F175–F184 (2007).
  • Callera GE, Tostes RC, Yogi A, Montezano AC, Touyz RM. Endothelin-1-induced oxidative stress in DOCA-salt hypertension involves NADPH-oxidase-independent mechanisms. Clin. Sci. (Lond.)110(2), 243–253 (2006).
  • Hirata Y, Emori T, Eguchi S et al. Endothelin receptor subtype B mediates synthesis of nitric oxide by cultured bovine endothelial cells. J. Clin. Invest.91, 1367–1373 (1993).
  • Penna C, Rastaldo R, Mancardi D et al. Effect of endothelins on the cardiovascular system. J. Cardiovasc. Med.7(9), 645–652 (2006).
  • Brunner F, Bras-Silva C, Cerdeira AS, Leite-Moreira AF. Cardiovascular endothelins: essential regulators of cardiovascular homeostasis. Pharmacol. Ther.111(2), 508–531 (2006).
  • Schiffrin EL. Vascular endothelin in hypertension. Vascul. Pharmacol.43(1), 19–29 (2005).
  • Touyz RM, Schiffrin EL. Role of endothelin in human hypertension. Can. J. Physiol. Pharmacol.81, 533–541 (2003).
  • Larivière R, Thibault G, Schiffrin EL. Increased endothelin-1 content in blood vessels of deoxycorticosterone acetate-salt hypertensive but not in spontaneously hypertensive rats. Hypertension21, 294–300 (1993).
  • Tostes RCA, David FL, Carvalho MHC, Nigro D, Scivoletto R, Fortes ZB. Gender differences in vascular reactivity to endothelin-1 in deoxycorticosterone acetate-salt hypertensive rats. J. Cardiovasc. Pharmacol.35(30 Suppl. 6), S99–S101 (2000).
  • Schiffrin EL, Larivière R, Li JS, Sventek P, Touyz RM. DOCA plus salt induces overexpression of vascular ET-1 and severe vascular hypertrophy in SHR. Hypertension25, 769–773 (1995).
  • Doucet J, Gonzalez W, Michel JB. Endothelin antagonists in salt-dependent hypertension associated with renal insufficiency. J. Cardiovasc. Pharmacol.27, 643–651 (1996).
  • Moreau P, d’Úscio LV, Takase H, Shaw S, Barton M, Lüscher TF. Angiotensin II increases tissue endothelin and induced vascular hypertrophy in vivo: reversal by ETA receptor antagonist. Circulation96, 1593–1597 (1997).
  • Sventek P, Turgeon A, Garcia R, Schiffrin EL. Vascular and cardiac overexpression of ET-1 gene in one kidney one clip Goldblatt hypertensive rats but only in the late phase of two-kidney one clip Goldblatt hypertension. J. Hypertens.14, 57–64 (1996).
  • Sharifi AM, He G, Touyz RM, Schiffrin EL. Vascular endothelin-1 gene expression and effect of an endothelin A receptor antagonist on structure and function of small arteries from stroke-prone spontaneously hypertensive rats. J. Cardiovasc. Pharmacol.31(Suppl. 1), S309–S312 (1998).
  • Touyz RM, Turgeon A, Schiffrin EL. Endothelin A receptor blockade improves renal function and doubles the life span of stroke-prone spontaneously hypertensive rats. J. Cardiovasc. Pharmacol.35(Suppl. 1), S300–S304 (2000).
  • Park JB, Schiffrin EL. ETA receptor antagonist prevents blood pressure elevation and vascular remodeling in aldosterone-infused rats. Hypertension37, 1444–1449 (2001).
  • Tostes RC, Touyz RM, He G, Chen X, Schiffrin EL. Contribution of ET-1 to renal AP-1 activation and macrophage infiltration in aldosterone-induced hypertension. Clin. Sci.103(Suppl. 48), 25S–30S (2002).
  • Ammarguellat FZ, Gannon PO, Amiri F, Schiffrin EL. Fibrosis, matrix metalloproteinases, and inflammation in the heart of DOCA-salt hypertensive rats: role of ETA receptors. Hypertension39, 679–684 (2002).
  • Verhagen AM, Rabelink TJ, Braam B et al. Endothelin A receptor blockade alleviates hypertension and renal lesions associated with chronic nitric oxide synthase inhibition. J. Am. Soc. Nephrol.9, 755–762 (1998).
  • Schiffrin EL. Endothelin. Potential role in hypertension and vascular hypertrophy. Hypertension25, 1135–1143 (1995).
  • Tostes RC, Touyz RM, He G, Ammarguellat F, Schiffrin EL. ETA receptor blockade decreases expression of growth factors and collagen and improves MMP-2 activity in kidneys from stroke-prone spontaneously hypertensive rats. J. Cardiovasc. Pharmacol.39, 892–900 (2002).
  • Gossl M, Lerman A. Endothelin: beyond a vasoconstrictor. Circulation113(9), 1156–1158 (2006).
  • King JM, Srivastava KD, Stefano GB, Bilfinger TV, Bahou WF, Magazine HI. Human monocyte adhesion is modulated by endothelin B receptor-coupled nitric oxide release. J. Immunol.158, 880–886 (1997).
  • Shimada K, Yonetani Y, Kita T, Suzumura A, Takanayagi T, Nakashima T. Cyclooxygenase 2 expression by endothelin-1-stimulated mouse resident peritoneal macrophages in vitro. Eur. J. Pharmacol.356, 73–80 (1998).
  • Ishizuka T, Takamizawa-Matsumoto M, Suzuki K, Kurita A. Endothelin-1 enhances vascular cell adhesion molecule-1 expression in tumor necrosis factor–stimulated vascular endothelial cells. Eur. J. Pharmacol.369, 237–245 (1999).
  • Finsnes F, Lyberg T, Christensen G, Skjønsberg OH. Effect of endothelin antagonism on the production of cytokines in eosinophilic airway inflammation. Am. J. Physiol.280, L659–L665 (2001).
  • Griswold DE, Douglas SA, Martin LD et al. Endothelin B receptor modulates inflammatory pain and cutaneous inflammation. Mol. Pharmacol.56, 807–812 (1999).
  • Cui P, Tani K, Kitamura H et al. A novel bioactive 31-amino acid endothelin-1 is a potent chemotactic peptide for human neutrophils and monocytes. J. Leukoc. Biol.70, 306–312 (2001).
  • Amiri F, Virdis A, Neves MF et al. Endothelium-restricted overexpression of human ET-1 causes vascular remodeling and endothelial dysfunction. Circulation110(15), 2233–2240 (2004).
  • Callera GE, Montezano AC, Touyz RM et al. ETA receptor blockade decreases adhesion molecule expression and cardiac injury in DOCA-salt hypertension. Hypertension43, 872–879 (2004).
  • Callera GE, Touyz RM, Teixeira SA et al. ETA receptor blockade decreases vascular superoxide generation in DOCA-salt hypertension. Hypertension42, 811–817 (2003).
  • Berrazueta JR, Bhagat K, Vallance P, MacAllister RJ. Dose- and time-dependency of the dilator effects of the endothelin antagonist, BQ-123, in the human forearm. Br. J. Clin. Pharmacol.44, 569–571 (1997).
  • Wilkinson IB, Webb DJ. Venous occlusion plethysmography in cardiovascular research: methodology and clinical applications. Br. J. Clin. Pharmacol.52, 631–646 (2001).
  • MacCarthy PA, Pegge NC, Prendergast BD, Shah AM, Groves PH. The physiological role of endogenous endothelin in the regulation of human coronary vasomotor tone. J. Am. Coll. Cardiol.37, 137–143 (2001).
  • Spratt JC, Goddard J, Patel N, Strachan FE, Rankin AJ, Webb DJ. Systemic ETA receptor antagonism with BQ-123 blocks ET-1 induced forearm vasoconstriction and decreases peripheral vascular resistance in healthy men. Br. J. Pharmacol.134, 648–654 (2001).
  • Verhaar MC, Strachan FE, Newby DE et al. Endothelin-A receptor antagonist-mediated vasodilatation is attenuated by inhibition of nitric oxide synthesis and by endothelin-B receptor blockade. Circulation97, 752–756 (1998).
  • Strachan FE, Spratt JC, Wilkinson IB, Johnston NR, Gray GA, Webb DJ. Systemic blockade of the endothelin-B receptor increases peripheral vascular resistance in healthy men. Hypertension33, 581–585 (1999).
  • Haynes WG, Hand M, Johnstone H, Padfield P, Webb DJ. Direct and sympathetically mediated venoconstriction in essential hypertension: enhanced response to endothelin-1. J. Clin. Invest.94, 1359–1364 (1994).
  • Schiffrin EL, Thibault G. Plasma endothelin in human essential hypertension. Am. J. Hypertens.4, 303–308 (1991).
  • Cardillo C, Kilcoyne CM, Cannon RO III, Panza JA. Interactions between nitric oxide and endothelin in the regulation of vascular tone of human resistance vessels in vivo. Hypertension35, 1237–1241 (2000).
  • Haynes WG, Ferro CJ, O’Kane KP, Somerville D, Lomax CC, Webb DJ. Systemic endothelin receptor blockade decreases peripheral vascular resistance and blood pressure in humans. Circulation93, 1860–1870 (1996).
  • Corder R, Carrier M, Khan N et al. Cytokine regulation of endothelin-1 release from bovine aortic endothelial cells. J. Cardiovasc. Pharmacol.26(Suppl. 3), S56–S58 (1995).
  • McCulloch KM, Docherty CC, Morecroft I et al. Endothelin B receptor-mediated contraction in human pulmonary resistance arteries. Br. J. Pharmacol.119, 1125–1130 (1996).
  • Channick RN, Sitbon O, Barst RJ, Manes A, Rubin LJ. Endothelin receptor antagonists in pulmonary arterial hypertension. J. Am. Coll. Cardiol.43, 62S–67S (2004).
  • Bauer M, Wilkens H, Langer F et al. Selective upregulation of endothelin B receptor gene expression in severe pulmonary hypertension. Circulation105, 1034–1036 (2002).
  • Fukuroda T, Fujikawa T, Ozaki S et al. Clearance of circulations endothelin-1 by ETB receptors in rats. Biochem. Biophys. Res. Commun.199, 1461–1465 (1994).
  • Russel FD, Molenaar P. The human heart endothelin system: ET-1 synthesis, storage, release and effect. Trends Pharmacol. Sci.21, 353–359 (2000).
  • Pacher R, Stanek B, Hulsmann M et al. Prognostic impact of big endothelin-1 plasma concentrations compared with invasive hemodynamic evaluation in severe heart failure. J. Am. Coll. Cardiol.27, 633–641 (1996).
  • Cody RJ, Haas GJ, Binkley PF et al. Plasma endothelin correlates with the extent of pulmonary hypertension in patients with chronic congestive heart failure. Circulation85, 504–509 (1992).
  • Hulsmann M, Stanek B, Frey B et al. Value of cardiopulmonary exercise testing and big endothelin plasma levels to predict short-term prognosis of patients with chronic heart failure. J. Am. Coll. Cardiol.32, 1695–1700 (1998).
  • Pönicke K, Vogelsang M, Heinroth M et al. Endothelin receptors in the failing and nonfailing human heart. Circulation97, 744–751 (1998).
  • Zolk O, Quattek J, Sitzler G et al. Expression of endothelin-1, endothelin-converting enzyme and endothelin receptors in chronic heart failure. Circulation99, 2118–2123 (1999).
  • Matsumura Y, Hashimoto N, Taira S et al. Different contributions of endothelin-A and endothelin-B receptors in the pathogenesis of deoxycorticosterone acetate-salt-induced hypertension in rats. Hypertension33, 759–765 (1999).
  • Matsumura Y, Kuro T, Kobayashi Y et al. Exaggerated vascular and renal pathology in endothelin-B receptor-deficient rats with deoxycorticosterone acetate-salt hypertension. Circulation102, 2765–2773 (2000).
  • Matsumura Y, Kuro T, Konishi F, Takaoka M, Gariepy CE, Yanagisawa M. Enhanced blood pressure sensitivity to DOCA-salt treatment in endothelin ET(B) receptor-deficient rats. Br. J. Pharmacol.129, 1060–1062 (2000).
  • Murakoshi N, Miyauchi T, Kakinuma Y et al. Vascular endothelin-B receptor system in vivo plays a favorable inhibitory role in vascular remodeling after injury revealed by endothelin-B receptor-knockout mice. Circulation106, 1991–1998 (2002).
  • Galie N, Manes A, Branzi A. The endothelin system in pulmonary arterial hypertension. Cardiovasc. Res.61, 227–237 (2004).
  • Ohuchi T, Kuwaki T, Ling GY et al. Elevation of blood pressure by genetic and pharmacological disruption of the ETB receptor in mice. Am. J. Physiol.276, R1071–R1077 (1999).
  • Reinhart GA, Preusser LC, Burke SE et al. Hypertension induced by blockade of ET(B) receptors in conscious nonhuman primates: role of ET(A) receptors. Am. J. Physiol.283, H1555–H1561 (2002).
  • Luft FC, Mervaala EMA, Muller DN et al. Hypertension-induced end-organ damage: a new transgenic approach to an old problem. Hypertension33, 212–218 (1999).
  • Muller DN, Mervaala EMA, Schmidt F et al. Effect of bosentan on NF-kB, inflammation, and tissue factor in angiotensin II-induced end-organ damage. Hypertension36, 282–293 (2000).
  • Luft FC. Proinflammatory effects of angiotensin II and endothelin: targets for progression of cardiovascular and renal diseases. Curr. Opin. Nephrol. Hypertens.11, 59–66 (2002).
  • Sasser JM, Pollock JS, Pollock DM. Renal endothelin in chronic angiotensin II hypertension. Am. J. Physiol.283, R243–R248 (2002).
  • Loffler BM. Endothelin-converting enzyme inhibitors: current status and perspectives. J. Cardiovasc. Pharmacol.35, S79–S82 (2000).
  • d’Uscio LV, Shaw S, Barton M, Luscher TF. Losartan but not verapamil inhibits angiotensin II-induced tissue endothelin increase: role of blood pressure and endothelial function. Hypertension31, 1305–1310 (1998).
  • Hernandez-Perera O, Perez-Sala D, Navarro-Antolin J et al. Effects of the 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors, atorvastatin and simvastatin, on the expression of endothelin-1 and endothelial nitric oxide synthase in vascular endothelial cells. J. Clin. Invest.101, 2711–2719 (1998).
  • Ikeda T, Ohta H, Okada M et al. Antihypertensive effects of a mixed endothelin-A- and -B-receptor antagonist, J-104132, were augmented in the presence of an AT1 -receptor antagonist, MK-954. J. Cardiovasc. Pharmacol.36, S337–S341 (2000).
  • Massart PE, Hodeige DG, Van Mechelen H et al. Angiotensin II and endothelin-1 receptor antagonists have cumulative hypotensive effects in canine Page hypertension. J. Hypertens.16, 835–841 (1998).
  • Iwanaga Y, Kihara Y, Inagaki K et al. Differential effects of angiotensin II versus endothelin-1 inhibitions in hypertrophic left ventricular myocardium during transition to heart failure. Circulation104, 606–612 (2001).
  • Molinaro G, Rouleau JL, Adam A. Vasopeptidase inhibitors: a new class of dual zinc metallopeptidase inhibitors for cardiorenal therapeutics. Curr. Opin. Pharmacol.2, 131–141 (2002).
  • Baranyi L, Campbell W, Ohshima K et al. Antisense homology box-derived peptides represent a new class of endothelin receptor inhibitors. Peptides19, 211–223 (1998).
  • Tiret L, Poirier O, Hallet V et al. The Lys198Asn polymorphism in the endothelin-1 gene is associated with blood pressure in overweight people. Hypertension33, 1169–1174 (1999).
  • Iglarz M, Benessiano J, Philip I et al. Preproendothelin-1 gene polymorphism is related to a change in vascular reactivity in the human mammary artery in vitro. Hypertension39, 209–213 (2002).
  • Agapitov AV, Haynes WG. A polymorphism in the endothelin-A receptor gene predicts survival in patients with idiopathic dilated cardiomyopathy. Eur. Heart J.22, 1948–1953 (2001).
  • Funalot B, Courbon D, Brousseau T et al.; EVA Study. Genes encoding endothelin-converting enzyme-1 and endothelin-1 interact to influence blood pressure in women: the EVA study. J. Hypertens.22, 739–743 (2004).
  • Krum H, Viskoper RJ, Lacourciere Y, Budde M, Charlon V. The effect of an endothelin receptor antagonist, bosentan, on blood pressure in patients with essential hypertension. N. Engl. J. Med.338, 784–790 (1998).
  • Black HR, El Shahawy M, Weiss RJ. Darusentan antihypertensive effect in patients with resistant hypertension. J. Am. Coll. Cardiol.47(4A), A915 (2006).
  • Hocher B, Schwarz A, Reinbacher D et al. Effects of endothelin receptor antagonists on the progression of diabetic nephropathy. Nephron87(2), 161–169 (2001).
  • Wu C, Decker ER, Blok N et al. Discovery, modeling, and human pharmacokinetics of N-(2-acetyl-4,6-dimethylphenyl)-3-(3,4-dimethylisoxazol-5-ylsulfamoyl)thiophene-2-carboxamide (TBC3711), a second generation, ETA selective, and orally bioavailable endothelin antagonist. J. Med. Chem.47, 1969–1986 (2004).
  • Nakov R, Pfarr E, Eberle S; HEAT Investigators. Darusentan: an effective endothelin A receptor antagonist for treatment of hypertension. Am. J. Hypertens.15, 583–589 (2002).
  • Williamson DJ, Wallman LL, Jones R et al. Hemodynamic effects of bosentan, an endothelin receptor antagonist, in patients with pulmonary hypertension. Circulation102, 411–418 (2000).
  • Channick RN, Simonneau G, Sitbon O et al. Effects of the dual endothelin-receptor antagonist bosentan in patients with pulmonary hypertension: a randomised placebo-controlled study. Lancet358, 1119–1123 (2001).
  • Rubin LJ, Badesch DB, Barst RJ et al. Bosentan therapy for pulmonary arterial hypertension. N. Engl. J. Med.346, 896–903 (2002).
  • Hiramoto Y, Shioyama W, Kuroda T et al. Effect of bosentan on plasma endothelin-1 concentration in patients with pulmonary arterial hypertension. Circ. J.71(3), 367–369 (2007).
  • Liu C, Chen J. Endothelin receptor antagonists for pulmonary arterial hypertension. Cochrane Database Syst. Rev.3, CD004434 (2006).
  • Barst RJ, Langleben D, Frost A et al.; STRIDE-1 Study Group. Sitaxsentan therapy for pulmonary arterial hypertension. Am. J. Respir. Crit. Care Med.169, 441–447 (2004).
  • Jacobs A, Preston IR, Gomberg-Maitland M. Endothelin receptor antagonism in pulmonary arterial hypertension – a role for selective ET(A) inhibition? Curr. Med. Res. Opin.22(12), 2567–2574 (2006).
  • Battistini B, Berthiaume N, Kelland NF, Webb DJ, Kohan DE. Profile of past and current clinical trials involving endothelin receptor antagonists: the novel “-sentan” class of drug. Exp. Biol. Med. (Maywood)231(6), 653–695 (2006).
  • Rich S, McLaughin VV. Endothelin receptor blockers in cardiovascular disease. Circulation108, 2184–2190 (2003).
  • Kalra PR, Moon JCC, Coats AJS. Do the results of the ENABLE (endothelium antagonist bosentan for lowering cardiac events in heart failure) study spell the end for non-selective endothelin antagonism in heart failure? Int. J. Cardiol.85, 195–197 (2002).
  • Coletta AP, Cleland JG. Clinical trials update: highlights of the Scientific Sessions of the XXIII Congress of the European Society of Cardiology – WARIS II, ESCAMI, PAFAC, RITZ-1 and TIME. Eur. J. Heart Fail.3, 747–750 (2001).
  • O’Connor CM, Gattis WA, Adams KF et al. Tezosentan in patients with acute heart failure and acute coronary syndromes. J. Am. Coll. Cardiol.41, 1452–1457 (2003).
  • Kaluski E, Kobrin I, Zimlichman R et al. RITZ-5 randomized intravenous tezosentan (an endothelin-A/B antagonist) for the treatment of pulmonary edema. J. Am. Coll. Cardiol.41, 204–210 (2003).
  • Luscher TF, Enseleit F, Pacher R et al. Hemodynamic and neurohumoral effects of selective endothelin (ET[A]) receptor blockade in chronic heart failure: the Heart failure ET(A) receptor blockade Trial (HEAT). Circulation106, 2666–2672 (2002).
  • Vatter H, Seifert V. Ambrisentan, a non-peptide endothelin receptor antagonist Cardiovasc. Drug Rev.24(1), 63–76 (2006).
  • Prasad SK, Dargie HJ, Smith GC et al. Comparison of the dual receptor endothelin antagonist enrasentan with enalapril in asymptomatic left ventricular systolic dysfunction: a cardiovascular magnetic resonance study. Heart92(6), 798–803 (2006).
  • Kelland NF, Webb DJ. Clinical trials of endothelin antagonists in heart failure: a question of dose? Exp. Biol. Med. (Maywood)231(6), 696–699 (2006).
  • Anand I, McMurray J, Cohn JN et al; EARTH investigators. Long-term effects of darusentan on left-ventricular remodelling and clinical outcomes in the Endothelin A Receptor antagonist Trial in Heart failure (EARTH): randomised, double-blind, placebo-controlled trial. Lancet364(9431), 347–354 (2004).
  • de Bold AJ, de Bold ML. Determinants of natriuretic peptide production by the heart: basic and clinical implications. J. Investig. Med.53(7), 371–377 (2005).
  • Dietz JR. Mechanisms of atrial natriuretic peptide secretion from the atrium. Cardiovasc. Res.68(1), 8–17 (2005).
  • Gunning M, Brenner BM. Urodilatin: a potent natriuretic peptide of renal origin. Curr. Opin. Nephrol. Hypertens.2, 857–862 (1993).
  • Vesely D, Douglass MA, Dietz JR et al. Three peptides from the atrial natriuretic factor prohormone amino terminus lower blood pressure and produce diuresis, natriuresis, and/or kaliuresis in humans. Circulation90, 1129–1140 (1994).
  • Chien KR, Knowlton KU, Zhu H, Chien S. Regulation of cardiac gene expression during myocardial growth and hypertrophy: molecular studies of adaptive physiological response. FASEB J.5, 3037–3046 (1991).
  • Sagnella GA. Measurement and significance of circulating natriuretic peptides in cardiovascular disease. Clin. Sci.95, 519–529 (1998).
  • Freitag MH, Larson MG, Levy D et al. Plasma brain natriuretic peptide levels and blood pressure tracking in the Framingham heart study. Hypertension41, 978–983 (2003).
  • Moe GW. B-type natriuretic peptide in heart failure. Curr. Opin. Cardiol.21(3), 208–214 (2006).
  • Furuya M, Yoshida M, Minamino N, Kangawa K, Matsuo H. C-type natriuretic peptide is a growth inhibitor of rat VSMCs. Biochem. Biophys. Res. Commun.177, 927–931 (1991).
  • Komatsu Y, Nakao K, Itoh H, Suga S, Ogawa Y, Imura H. Vascular natriuretic peptide. Lancet34, 622 (1992).
  • Kalra PR, Anker SD, Struthers AD, Coats AJ. The role of C-type natriuretic peptide in cardiovascular medicine. Eur. Heart J.22, 997–1007 (2001).
  • Kohno M, Horio T, Yokokawa K, Kurihara N, Takeda T. C-type natriuretic peptide inhibits thrombin and angiotensin II stimulated endothelin release via cyclic guanosine 3´,5´-monophosphate. Hypertension19, 320–325 (1992).
  • Mutafova-Yambolieva VN, Westfall DP. Modulatory effects of C-type natriuretic peptide on sympathetic cotransmission in the rat isolated tail artery. Clin. Exp. Pharmacol. Physiol.25, 1013–1017 (1998).
  • Koller KJ, Goeddel DV. Molecular biology of the natriuretic peptides and their receptors. Circulation86, 1081–1088 (1992).
  • Charles CJ, Espiner EA, Nicholls MG et al. Clearance receptors and endopeptidase 24.11: equal role in natriuretic peptide metabolism in conscious sheep. Am. J. Physiol.271, R373–R380 (1996).
  • Kenny AJ, Bourne A, Ingram J. Hydrolysis of human and pig brain natriuretic peptides, urodilatin, C-type natriuretic peptide and some C-receptor ligands by endopeptidase 24.11. Biochem. J.291, 83–88 (1993).
  • Marin-Grez M, Fleming JT, Steihausen M. Atrial natriuretic peptide causes pre-glomerular vasodilation and post-glomerular vasoconstriction in rat kidney. Nature324, 473–476 (1986).
  • Anand-Srivastava MB, Sairam MR, Cantin M. Ring-deleted analogs of atrial natriuretic factor inhibit adenylate cyclase/cAMP system. Possible coupling of clearance atrial natriuretic factor receptors to adenylate cyclase/cAMP signal transduction system. J. Biol. Chem.265, 8566–8572 (1990).
  • Maack T, Tikonova LN, Friedman O, Cohen D. Functional properties and dynamics of natriuretic peptide receptors. Proc. Soc. Exp. Biol. Med.213, 109–116 (1996).
  • Nakao K, Sugawara A, Mori N et al. The pharmacokinetics of α-human atrial natriuretic polypeptide in healthy subjects. Eur. J. Clin. Pharmacol.31, 101–103 (1986).
  • Stockand JD, Sansom SC. Regulation of filtration rate by glomerular mesangial cells in health and diabetic renal disease. Am. J. Kidney Dis.29, 971–981 (1997).
  • Sonnenberg H, Honrath U, Chong CK, Wilson DR. Atrial natriuretic factor inhibits sodium transport in medullary collecting duct. Am. J. Physiol.231, 1572–1573 (1986).
  • Harris PJ, Thomas D, Morgan TO. Atrial natriuretic peptide inhibits angiotensin-stimulated proximal tubular sodium and water reabsorption. Nature326, 697–698 (1987).
  • Dillingham MA, Anderson RJ. Inhibition of vasopressin action by atrial natriuretic factor. Science250, F963–F966 (1986).
  • Volpe M, Mele AF, Indolfi C et al. Hemodynamic and hormonal effects of atrial natriuretic factor in patients with essential hypertension. J. Am. Coll. Cardiol.10, 787–793 (1987).
  • Volpe M, Sosa RE, Muller FB et al. Differing hemodynamic and hormonal effects of human α atrial natriuretic peptide in two models of hypertension. Am. J. Physiol.250, H871–H878 (1986).
  • Volpe M, Cuocolo A, Vecchione F et al. Influence of volume expansion on hemodynamic effects of atrial natriuretic factor in rabbits. Am. J. Physiol.256, H852–H858 (1989).
  • Volpe M, Lembo G, Condorelli GL et al. Converting enzyme inhibition prevents the effect of atrial natriuretic factor on baroreflex responses in humans. Circulation82, 1214–1221 (1990).
  • Yang RH, Jin HK, Wyss JM, Chen YF, Oparil S. Pressor effect of blocking atrial natriuretic peptide in nucleus tractus solitari. Hypertension19, 198–205 (1992).
  • Itoh H, Pratt RE, Dzau VJ. Atrial natriuretic polypeptide inhibits hypertrophy of vascular smooth muscle cells. J. Clin. Invest.86, 1690–1697 (1990).
  • Vesely DL. Atrial natriuretic peptides in pathophysiological diseases. Cardiovasc. Res.51, 647–658 (2001).
  • Vesely DL, Arnold WC, Winters CJ, Sallman AL, Rico DM. Increased circulating concentration of the N-terminus of the atrial natriuretic prohormone in persons with pheochromocytoma. J. Clin. Endocrinol. Metab.71, 1138–1146 (1990).
  • Steinhelper ME, Cochrane KL, Field LJ. Hypotension in transgenic mice expressing atrial natriuretic factor fusion genes. Hypertension16, 301–307 (1990).
  • Ogawa Y, Itoh H, Tamura N et al. Molecular cloning of the complementary DNA and gene that encode mouse brain natriuretic peptide and generation of transgenic mice that overexpress the brain natriuretic peptide gene J. Clin. Invest.93, 1911–1921 (1994).
  • Jhon SWM, Krege JH, Oliver PM et al. Genetic decreases in atrial natriuretic peptide and salt sensitive hypertension. Science267, 679–681 (1995).
  • Lopez MJ, Wong SK-F, Kishimoto I et al. Salt-resistant hypertension in mice lacking the guanyl cyclase-A receptor for atrial natriuretic peptide. Nature378, 65–68 (1995).
  • Yokota N, Bruneau BG, Kuroski T, de Bold ML, de Bold AJ. Atrial natriuretic factor significantly contributes to the mineralocorticoid escape phenomenon: evidence for a guanylate cyclase-mediated pathway. J. Clin. Invest.94, 1938–1946 (1994).
  • Rubattu S, Volpe M. The atrial natriuretic peptide: a changing view. J. Hypertens.19, 1923–1931 (2001).
  • Estrada D, Tellez MJ, Moya J, Fernandez-Durango R, Egido J, Fernandez-Cruz A. High plasma levels of endothelin-1 and atrial natriuretic peptide in patients with acute ischemic stroke. Am. J. Hypertens.7, 1085–1089 (1994).
  • Rubattu S, Ridker PM, Stampfer JM, Volpe M, Hennekens CH, Lindpaintner K. The gene encoding atrial natriuretic peptide and the risk of human stroke. Circulation100, 1722–1726 (1999).
  • Rubattu S, Volpe M, Kreutz R, Ganten U, Ganten D, Lindpaintner K. Chromosomal mapping of quantitative trait loci contributing to stroke in an animal model of complex human disease. Nat. Genet.13, 429–434 (1996).
  • Rubattu S, Lee MA, De Paolis P et al. Altered structure regulation an function of the gene encoding atrial natriuretic peptide in the stroke-prone spontaneously hypertensive rat. Circ. Res.85, 900–905 (1999).
  • Rubattu S, Giliberti R, Ganten U, Volpe M. A differential brain atrial natriuretic peptide expression co-segregates with occurrence of early stroke in the stroke prone phenotype of spontaneously hypertensive rat. J. Hypertens.17, 1849–1852 (1999).
  • Sagnella GA. Atrial natriuretic peptide mimetics and vasopeptidase inhibitors. Cardiovasc. Res.51, 416–428 (2001).
  • Mitchell GF, Izzo JL, Lacourcière Y et al. Omapatrilat reduces pulse pressure and proximal aortic stiffness in patients with systolic hypertension. Results of the Conduit Hemodynamics of Omapatrilat International Research study. Circulation105, 2955–2961 (2002).
  • Kusserow H, Unger T. Vasoactive peptides, their receptors and drug development. Basic Clin. Pharmacol. Toxicol.94, 5–12 (2004).
  • Corti R, Burnett JC, Rouleau JL, Ruschitzka F, Lüscher TF. Vasopeptidase inhibitors. A new therapeutic concept in cardiovascular disease? Circulation104, 1856–1862 (2001).
  • Campbell DJ. Vasopeptidase inhibition. A double-edged sword? Hypertension41, 383–389 (2001).
  • Dorsch MP, Rodgers JE. Nesiritide: harmful or harmless? Pharmacotherapy26(10), 1465–1478 (2006).
  • Dumoulin MJ, Lamontagne D, Molinaro G, Adam A. Omapatrilat: a new tool for understanding metabolism of bradykinin at the endothelium level. Curr. Hypertens. Rep.3(Suppl. 2), S28–S30 (2001).
  • Rapport MM, Green AA, Page IH. Crystalline serotonin. Science108, 329–330 (1948).
  • Jacobs BL, Azmitia EC. Structure and function of the brain serotonin system. Physiol. Rev.72(1), 165–229 (1972).
  • Gershon MD. Roles played by 5-hydroxytryptamine in the physiology of the bowel. Aliment. Pharmacol. Ther.13(Suppl. 2), 15–30 (1999).
  • Cote F, Fligny C, Fromes Y, Mallet J, Vodjdani G. Recent advances in understanding serotonin regulation of cardiovascular function. Trends Mol. Med.10(5), 232–238 (2004).
  • Fishkes H, Rudnick G. Bioenergetics of serotonin transport by membrane vesicles derived from platelet dense granules. J. Biol. Chem.257(10), 5671–5677 (1982).
  • Cicin-Sain L, Frobe A, Jernej B. Physiological characteristics of serotonin transporters on rat platelets. Comp. Biochem. Physiol.120(4), 723–729 (1998).
  • Dodson AM, Anderson GM, Rhoden KJ. Serotonin uptake and metabolism by cultured guinea pig airway smooth muscle cells. Pulm. Pharmacol. Ther.17(1), 19–25 (2004).
  • Walther DJ, Peter JU, Bashammakh S et al. Synthesis of serotonin by a second tryptophan hydroxylase isoform. Science299(5603), 76–79 (2003).
  • Martin GR, Eglen RM, Hamblin MW, Hoyer D, Yocca F. The structure and signalling properties of 5-HT receptors: an endless diversity? Trends Pharmacol. Sci.19, 2–4 (1998).
  • Peroutka SJ. 5-HT receptors: past, present and future. Trends Neurosci.18, 68–69 (1995).
  • Sprang SR. G protein mechanisms: insights from structural analysis. Annu. Rev. Biochem.66, 639–678 (1997).
  • Raymond JR, Mukhin YV, Gelasco A et al. Multiplicity of mechanisms of serotonin receptor signal transduction. Pharmacol. Ther.92(2–3), 179–212 (2001).
  • Hoyer D, Clarke DE, Fozard JR et al. International Union of Pharmacology classification of receptors for 5-hydroxytryptamine (Serotonin). Pharmacol. Rev.46, 157–203 (1994).
  • Wesolowska A. In the search for selective ligands of 5-HT5, 5-HT6 and 5-HT7 serotonin receptors. Pol. J. Pharmacol.54(4), 327–341 (2002).
  • Noda M, Higashida H, Aoki S, Wada K. Multiple signal transduction pathways mediated by 5-HT receptors. Mol. Neurobiol.9(1), 31–39 (2004).
  • Richardson BP, Engel G, Donatsch P, Stadler PA. Identification of serotonin M-receptor subtypes and their specific blockade by a new class of drugs. Nature316(6024), 126–131 (1985).
  • Ullmer C, Schmuck K, Kalkman HO, Lubbert H. Expression of serotonin receptor mRNAs in blood vessels. FEBS Lett.70(3), 215–221 (1995).
  • Ishida T, Hirata K, Sakoda T, Kawashima S, Akita H, Yokoyama M. Identification of mRNA for 5-HT1 and 5-HT2 receptor subtypes in human coronary arteries. Cardiovasc. Res.41(1), 267–274 (1999).
  • Verheggen R, Hundeshagen AG, Brown AM, Schindler M, Kaumann AJ. 5-HT1B receptor-mediated contractions in human temporal artery: evidence from selective antagonists and 5-HT receptor mRNA expression. Br. J. Pharmacol.124, 1345–1354 (1998).
  • Watts SW, Yang P, Banes AK, Baez M: Activation of ERK mitogen-activated protein kinase proteins by vascular serotonin receptors J. Cardiovasc. Pharmacol.8, 539–551 (2001).
  • Lovern F, Li XF, Lytton J, Triggle C. Functional characterization of mRNA expression of 5-HT receptors mediating contraction in human umbilical artery. Br. J. Pharmacol.127, 1247–1255 (1999).
  • Morecroft I, Heeley RP, Prentice HM, Kirk A, MacLean MR. 5-hydroxytryptamine receptors mediating contraction in human small muscular pulmonary arteries: importance of the 5-HT1B receptor. Br. J. Pharmacol.128, 730–734 (1999).
  • Morecroft I, MacLean MR. 5-hydroxytryptamine receptors mediating vasoconstriction and vasodilation in perinatal and adult rabbit small pulmonary arteries. Br. J. Pharmacol.125(1), 69–78 (1998).
  • Kaumann AJ, Frenken M, Posival H, Brown AM. Variable participation of 5-HT1-like receptors and 5-HT2 receptors in serotonin-induced contraction of human isolated coronary arteries. 5-HT1-like receptors resemble cloned 5-HT1D β receptors. Circulation90(3), 1141–1153 (1994).
  • De Vries P, Willems EW, Heiligers JP, Villalon CM, Saxena PR. Investigation of the role of 5-HT1B and 5-HT1D receptors in the sumatriptan-induced constriction of porcine carotid arteriovenous anastomoses. Br. J. Pharmacol.127(2), 405–412 (1999).
  • Watts SW, Thompson JM. Characterization of the contractile 5-hydroxytryptamine receptor in the renal artery of the normotensive rat. J. Pharmacol. Exp. Ther.309(1), 165–172 (2004).
  • MacLean MR, Sweeney G, Baird M, McCulloch KM, Houslay M, Morecroft I. 5-hydroxytryptamine receptors mediating vasoconstriction in pulmonary arteries from control and pulmonary hypertensive rats. Br. J. Pharmacol.119, 917–930 (1996).
  • Choppin A, O’Connor SE. Presence of vasoconstrictor 5HT1-like receptors revealed by precontraction of rabbit isolated mesenteric artery. Br. J. Pharmacol.114(2), 309–314 (1995).
  • Berridge MJ, Bootman MD, Roderick HL. Calcium signalling: dynamics, homeostasis and remodelling. Nat. Rev. Mol. Cell Biol.4(7), 517–529 (2003).
  • Yang CM, Chiu CT, Fan LW, Tsao HL, Wang CC. Regulation of 5-hydroxytryptamine-induced signal transduction in canine cultured aorta smooth muscle cells by phorbol ester. Cell Signal11(8), 581–589 (1999).
  • Yuan XJ, Bright RT, Aldinger AM, Rubin LJ. Nitric oxide inhibits serotonin-induced calcium release in pulmonary artery smooth muscle cells. Am. J. Physiol.272, L44–L50 (1997).
  • Hill PB, Dora KA, Hughes AD, Garland CJ. The involvement of intracellular Ca(2+) in 5-HT(1B/1D) receptor-mediated contraction of the rabbit isolated renal artery. Br. J. Pharmacol.130(4), 835–842 (2000).
  • Jackson WF. Ion channels and vascular tone. Hypertension35(1 Pt 2), 173–178 (2000).
  • Broad LM, Cannon TR, Taylor CW. A non-capacitative pathway activated by arachidonic acid is the major Ca2+ entry mechanism in rat A7r5 smooth muscle cells stimulated with low concentrations of vasopressin. J. Physiol.517, 121–134 (1999).
  • Meves H. Modulation of ion channels by arachidonic acid. Prog. Neurobiol.43, 175–186 (1994).
  • Guibert C, Marthan R, Savineau JP. 5-HT induces an arachidonic acid-sensitive calcium influx in rat small intrapulmonary artery. Am. J. Physiol.286(6), L1228–L1236 (2004).
  • Vanhoenacker P, Haegeman G, Leysen JE. 5-HT7 receptors: current knowledge and future prospects. Trends Pharmacol. Sci.21(2), 70–77 (2000).
  • Terrón JA. The relaxant 5-HT receptor in the dog coronary artery smooth muscle: pharmacological resemblance to the cloned 5-HT7 receptor subtype. Br. J. Pharmacol.118, 1421–1428 (1996).
  • Terrón JA, Falcón-Neri A. Pharmacological evidence for the 5-HT7 receptor mediating smooth muscle relaxation in canine cerebral arteries. Br. J. Pharmacol.127, 609–616 (1999).
  • Martin GR, Wilson RJ. Operational characteristics of a 5-HT receptor mediating direct vascular relaxation: identity with 5-HT7 receptors? Br. J. Pharmacol.114, 383P (1995).
  • Weinshank RL, Zgombick JM, Macchi MJ, Branchek TA, Hartig PR. Human serotonin 1D receptor is encoded by a subfamily of two distinct genes: 5-HT1D α and 5-HT1D β. Proc. Natl Acad. Sci. USA89(8), 3630–3634 (1992).
  • Schoeffter P, Ullmer C, Gutierrez M, Weitz-Schmidt G, Lubbert H. Functional serotonin 5-HT1D receptors and 5-HT1D β receptor mRNA expression in human umbilical vein endothelial cells. Naunyn Schmiedebergs Arch. Pharmacol.352(5), 580–582 (1995).
  • Flavahan NA, Shimokawa H, Vanhoutte PM. Pertussis toxin inhibits endothelium-dependent relaxations to certain agonists in porcine coronary arteries. J. Physiol.408, 549–560 (1989).
  • Potenza MA, Serio M, Montagnani M et al. Functional evaluation of 5-hydroxytryptamine receptor activity in rat resistance vessels. J. Auton. Pharmacol.18(2), 75–81 (1998).
  • Gupta P. An endothelial 5-HT receptor that mediates relaxation in guinea-pig isolated jugular vein resembles the 5-HT1D subtype. Br. J. Pharmacol.106(3), 703–709 (1992).
  • Choi DS, Birraux G, Launay JM, Maroteaux L. The human serotonin 5-HT2B receptor: pharmacological link between 5-HT2 and 5-HT1D receptors. FEBS Lett.352(3), 393–399 (1994).
  • McDuffie JE, Coaxum SD, Maleque MA. 5-hydroxytryptamine evokes endothelial nitric oxide synthase activation in bovine aortic endothelial cell cultures. Proc. Soc. Exp. Biol. Med.221(4), 386–390 (1999).
  • Lee SL, Wang WW, Lanzillo JJ, Fanburg BL. Regulation of serotonin-induced DNA synthesis of bovine pulmonary artery smooth muscle cells. Am. J. Physiol.266(1 Pt 1), L53–L60 (1994).
  • Saxena PR, Villalon CM. Cardiovascular effects of serotonin agonists and antagonists. J. Cardiovasc. Pharmacol.15(7), S17–S34 (1990).
  • Lee SL, Wang WW, Lanzillo JJ, Fanburg BL. Serotonin produces both hyperplasia and hypertrophy of bovine pulmonary artery smooth muscle cells in culture. Am. J. Physiol.266(1 Pt 1), L46–L52 (1994).
  • Kelleher MD, Abe MK, Chao T-SO et al. Role of MAP kinase activation in bovine tracheal smooth muscle mitogenesis. Am. J. Physiol.268, L894–L901 (1995).
  • Watts SW. Serotonin activates the mitogen-activated protein kinase pathway in vascular smooth muscle: use of the mitogen-activated protein kinase kinase inhibitor PD098059. J. Pharmacol. Exp. Ther.279(3), 1541–1550 (1996).
  • Banes AK, Loberg RD, Brosius FC 3rd, Watts SW. Inability of serotonin to activate the c-Jun N-terminal kinase and p38 kinase pathways in rat aortic vascular smooth muscle cells. BMC Pharmacol.1(1), 8 (2001).
  • McKune CM, Watts SW. Characterization of the serotonin receptor mediating contraction in the mouse thoracic aorta and signal pathway coupling. J. Pharmacol. Exp. Ther.297(1), 88–95 (2001).
  • Florian JA, Watts SW. Integration of mitogen-activated protein kinase kinase activation in vascular 5-hydroxytryptamine 2A receptor signal transduction. J. Pharmacol. Exp. Ther.284(1), 346–355 (1998).
  • Lee SL, Wang WW, Lanzillo JJ, Fanburg BL. Regulation of serotonin-induced DNA synthesis of bovine pulmonary artery smooth muscle cells. Am. J. Physiol.266(1 Pt 1), L53–L60 (1994).
  • Ni W, Thompson JM, Northcott CA, Lookingland K, Watts SW. The serotonin transporter is present and functional in peripheral arterial smooth muscle. J. Cardiovasc. Pharmacol.43(6), 770–781 (2004).
  • Eddahibi S, Fabre V, Boni C et al. Induction of serotonin transporter by hypoxia in pulmonary vascular smooth muscle cells. Relationship with the mitogenic action of serotonin. Circ. Res.84(3), 329–336 (1999).
  • Lee SL, Wang WW, Fanburg BL. Association of Tyr phosphorylation of GTPase-activating protein with mitogenic action of serotonin. Am. J. Physiol.272, C223–C230 (1997).
  • Touyz RM. Molecular and cellular mechanisms in vascular injury in hypertension: role of angiotensin II. Curr. Opin. Nephrol. Hypertens.14(2), 125–131 (2005).
  • Yusuf S, Al-Saady N, Camm AJ. 5-hydroxytryptamine and atrial fibrillation: how significant is this piece in the puzzle? J. Cardiovasc. Electrophysiol.14, 209–214 (2003).
  • Watts SW. 5-HT in systemic hypertension: foe, friend or fantasy? Clin. Sci.108, 399–412 (2005).
  • Ni W, Watts SW. 5-hydroxytryptamine in the cardiovascular system: focus on the serotonin transporter (SERT). Clin. Exp. Pharmacol. Physiol.33(7), 575–583 (2006).
  • Doggrell SA. The role of 5-HT on the cardiovascular and renal systems and the clinical potential of 5-HT modulation. Expert Opin. Investig. Drugs12(5), 805–823 (2003).
  • Watts SW. Serotonin-induced contraction in mesenteric resistance arteries: signaling and changes in deoxycorticosterone acetate-salt hypertension. Hypertension39(3), 825–829 (2002).
  • Banes AK, Watts SW. Enhanced contraction to 5-hydroxytryptamine is not due to ‘unmasking’ of 5-hydroxytryptamine(1b) receptors in the mesenteric artery of the deoxycorticosterone acetate-salt rat. Hypertension38(4), 891–895 (2001).
  • Banes AK, Watts SW. Upregulation of arterial serotonin 1B and 2B receptors in deoxycorticosterone acetate-salt hypertension. Hypertension39(2 Pt 2), 394–398 (2002).
  • Banes AK, Watts SW. Arterial expression of 5-HT2B and 5-HT1B receptors during development of DOCA-salt hypertension. BMC Pharmacol.3(1), 12–14 (2003).
  • Watts SW, Fink GD. 5-HT2B-receptor antagonist LY-272015 is antihypertensive in DOCA-salt-hypertensive rats. Am. J. Physiol.276(3 Pt 2), H944–H952 (1999).
  • Watts SW. 5-Hydroxytryptamine-induced potentiation of endothelin-1- and norepinephrine-induced contraction is mitogen-activated protein kinase pathway dependent. Hypertension35(1 Pt 2), 244–248 (2000).
  • Eddahibi S, Humbert M, Fadel E et al. Serotonin transporter overexpression is responsible for pulmonary artery smooth muscle hyperplasia in primary pulmonary hypertension. J. Clin. Invest.108(8), 1141–1150 (2001).
  • MacLean MR, Herve P, Eddahibi S, Adnot S. 5-hydroxytryptamine and the pulmonary circulation: receptors, transporters and relevance to pulmonary arterial hypertension. Br. J. Pharmacol.131(2), 161–168 (2000).
  • Eddahibi S, Hanoun N, Lanfumey L et al. Attenuated hypoxic pulmonary hypertension in mice lacking the 5-hydroxytryptamine transporter gene. J. Clin. Invest.105(11), 1555–1562 (2000).
  • Marcos E, Adnot S, Pham MH et al. Serotonin transporter inhibitors protect against hypoxic pulmonary hypertension. Am. J. Respir. Crit. Care Med.168(4), 487–493 (2003).
  • Launay JM, Herve P, Peoc’h K et al. Function of the serotonin 5-hydroxytryptamine 2B receptor in pulmonary hypertension. Nat. Med.8(10), 1129–1135 (2002).
  • Nebigil CG, Jaffre F, Messaddeq N et al. Overexpression of the serotonin 5-HT2B receptor in heart leads to abnormal mitochondrial function and cardiac hypertrophy. Circulation107(25), 3223–3229 (2003).
  • Sari Y, Zhou FC. Serotonin and its transporter on proliferation of fetal heart cells. Int. J. Dev. Neurosci.21, 417–424 (2003).
  • Nebigil CG, Choi DS, Dierich A et al. Serotonin 2B receptor is required for heart development. Proc. Natl Acad. Sci. USA97(17), 9508–9513 (2000).
  • Cote F, Thevenot E, Fligny C et al. Disruption of the nonneuronal tph1 gene demonstrates the importance of peripheral serotonin in cardiac function. Proc. Natl Acad. Sci. USA100(23), 13525–13530 (2003).
  • McEnroe JD, Fleishaker JC. Clinical pharmacokinetics of almotriptan, a serotonin 5-HT(1B/1D) receptor agonist for the treatment of migraine. Clin. Pharmacokinet.44(3), 237–246 (2005).
  • Berends AC, Luiten PG, Nyakas C. A review of the neuroprotective properties of the 5-HT1A receptor agonist repinotan HCl (BAYx3702) in ischemic stroke. CNS Drug Rev.11(4), 379–402 (2005).
  • Nagatomo T, Rashid M, Abul Muntasir H, Komiyama T. Functions of 5-HT2A receptor and its antagonists in the cardiovascular system. Pharmacol. Ther.104(1), 59–81 (2004).
  • Terron JA. Is the 5-HT(7) receptor involved in the pathogenesis and prophylactic treatment of migraine? Eur. J. Pharmacol.439(1–3), 1–11 (2002).
  • Goadsby PJ. Serotonin receptor ligands: treatments of acute migraine and cluster headache. Handb. Exp. Pharmacol.177, 129–143 (2007).
  • Takiya L, Piccininni LC, Kamath V. Safety and efficacy of eletriptan in the treatment of acute migraine. Pharmacotherapy26(1), 115–128 (2006).

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