Abstract
Hypertension is a well-known risk factor for atherosclerosis, but the molecular mechanisms that link elevated blood pressure to the progression of atherosclerosis remain unclear. Human urotensin II (U-II), the most potent endogenous vasoconstrictor peptide identified to date, and its receptor (UT receptor) are involved in the etiology of essential hypertension. In patients with essential hypertension, U-II infused into the forearm brachial artery has been shown to induce vasoconstriction. Recent studies have demonstrated elevated plasma U-II concentrations in patients with essential hypertension, diabetes mellitus, atherosclerosis, and coronary artery disease. U-II is expressed in endothelial cells, macrophages, macrophage-derived foam cells, and myointimal and medial vascular smooth muscle cells (VSMCs) of atherosclerotic human coronary arteries. UT receptors are present in VSMCs of human coronary arteries, the thoracic aorta and cardiac myocytes. Lymphocytes are the most active producers of U-II, whereas monocytes and macrophages are the major cell types expressing UT receptors, with relatively little receptor expression in foam cells, lymphocytes, and platelets. U-II accelerates foam cell formation by up-regulation of acyl-coenzyme A:cholesterol acyltransferase-1 in human monocyte-derived macrophages. In human endothelial cells, U-II promotes cell proliferation and up-regulates type 1 collagen expression. U-II also activates nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and plasminogen activator inhibitor-1 in human VSMCs, and stimulates VSMC proliferation with synergistic effects observed when combined with oxidized low-density lipoprotein, lysophosphatidylcholine, reactive oxygen species or serotonin. These findings suggest that U-II plays key roles in accelerating the development of atherosclerosis, thereby leading to coronary artery disease.
Similar content being viewed by others
Article PDF
References
Wilson PW, D'Agostino RB, Levy D, Belanger AM, Silbershatz H, Kannel WB : Prediction of coronary heart disease using risk factor categories. Circulation 1998; 97: 1837–1847.
Psaty BM, Furberg CD, Kuller LH, et al: Association between blood pressure level and the risk of myocardial infarction, stroke, and total mortality: the cardiovascular health study. Arch Intern Med 2001; 161: 1183–1192.
Domanski M, Mitchell G, Pfeffer M, et al: Pulse pressure and cardiovascular disease–related mortality: follow-up study of the Multiple Risk Factor Intervention Trial (MRFIT). JAMA 2002; 287: 2677–2683.
Mancia G, Parati G, Hennig M, et al: Relation between blood pressure variability and carotid artery damage in hypertension: baseline data from the European Lacidipine Study on Atherosclerosis (ELSA). J Hypertens 2001; 19: 1981–1989.
Chobanian AV, Lichtenstein AH, Nilakhe V, Haudenschild CC, Drago R, Nickerson C : Influence of hypertension on aortic atherosclerosis in the Watanabe rabbit. Hypertension 1989; 14: 203–209.
Tropea BI, Huie P, Cooke JP, Tsao PS, Sibley RK, Zarins CK : Hypertension-enhanced monocyte adhesion in experimental atherosclerosis. J Vasc Surg 1996; 23: 596–605.
Furumoto T, Saito N, Dong J, Mikami T, Fujii S, Kitabatake A : Association of cardiovascular risk factors and endothelial dysfunction in Japanese hypertensive patients: implications for early atherosclerosis. Hypertens Res 2002; 25: 475–480.
Curmi PA, Juan L, Tedgui A : Effect of transmural pressure on low density lipoprotein and albumin transport and distribution across the intact arterial wall. Circ Res 1990; 66: 1692–1702.
Santilli SM, Fiegel VD, Knighton DR : Changes in the aortic wall oxygen tensions of hypertensive rabbits. Hypertension 1992; 19: 33–39.
Crawford DW, Blankenhorn DH : Arterial wall oxygenation, oxyradicals, and atherosclerosis. Atherosclerosis 1991; 89: 97–108.
Watanabe T, Pakala R, Katagiri T, Benedict CR : Antioxidant N-acetylcysteine inhibits vasoactive agents–potentiated mitogenic effect of mildly oxidized LDL on vascular smooth muscle cells. Hypertens Res 2002; 25: 311–314.
Takeuchi H, Saitoh S, Takagi S, et al: Metabolic syndrome and cardiac disease in Japanese men: applicability of the concept of metabolic syndrome defined by the National Cholesterol Education Program–Adult Treatment Panel III to Japanese men—the Tanno and Sobetsu Study. Hypertens Res 2005; 28: 203–208.
Griendling KK, Sorescu D, Ushio-Fukai M : NAD(P)H oxidase: role in cardiovascular biology and disease. Circ Res 2000; 86: 494–501.
Hozawa A, Ebihara S, Ohmori K, et al: Increased plasma 8-isoprostane levels in hypertensive subjects: the Tsurugaya project. Hypertens Res 2004; 27: 557–561.
Maggi E, Marchesi E, Ravetta V, Martignoni A, Finardi G, Bellomo G : Presence of autoantibodies against oxidatively modified low-density lipoprotein in essential hypertension: a biochemical signature of an enhanced in vivo low-density lipoprotein oxidation. J Hypertens 1995; 13: 129–138.
Frostegard J, Wu R, Lemne C, Thulin T, Witztum JL, Faire U : Circulating oxidized low-density lipoprotein is increased in hypertension. Clin Sci (Lond) 2003; 105: 615–620.
Ames RS, Sarau HM, Douglas SA, et al: Human urotensin II is a potent vasoconstrictor and agonist for the orphan receptor GPR14. Nature 1999; 401: 282–286.
Watanabe T, Suguro T, Miyazaki A, et al: Human urotensin II accelerates foam cell formation in human monocyte-derived macrophages. Hypertension 2005; 46: 738–744.
Watanabe T, Pakala R, Katagiri T, Benedict CR : Synergistic effect of urotensin II with mildly oxidized LDL on DNA synthesis in vascular smooth muscle cells. Circulation 2001; 104: 16–18.
Watanabe T, Pakala R, Katagiri T, Benedict CR : Synergistic effect of urotensin II with serotonin on vascular smooth muscle cell proliferation. J Hypertens 2001; 19: 2191–2196.
Watanabe T, Kanome T, Suguro T, Miyazaki A : Human urotensin II and metabolic syndrome. Vascular Disease Prevention 2006; 3: 91–98.
Cheung BM, Leung R, Man YB, Wong LY : Plasma concentration of urotensin II is raised in hypertension. J Hypertens 2004; 22: 1341–1344.
Matsushita M, Shichiri M, Imai T, et al: Co-expression of urotensin II and its receptor (GPR14) in human cardiovascular and renal tissues. J Hypertens 2001; 19: 2185–2190.
Totsune K, Takahashi K, Arihara Z, Sone M, Ito S, Murakami O : Increased plasma urotensin II levels in patients with diabetes mellitus. Clin Sci (Lond) 2003; 104: 1–5.
Totsune K, Takahashi K, Arihara Z, et al: Elevated plasma levels of immunoreactive urotensin II and its increased urinary excretion in patients with type 2 diabetes mellitus: association with progress of diabetic nephropathy. Peptides 2004; 25: 1809–1814.
Suzuki S, Wenyi Z, Hirai M, et al: Genetic variations at urotensin II and urotensin II receptor genes and risk of type 2 diabetes mellitus in Japaneses. Peptides 2004; 25: 1803–1808.
Langham RG, Kelly DJ, Gow RM, et al: Increased expression of urotensin II and urotensin II receptor in human diabetic nephrophathy. Am J Kidney Dis 2004; 44: 826–831.
Takahashi K : Translational medicine in fish-derived peptides: from fish endocrinology to human physiology and diseases. Endocr J 2004; 51: 1–17.
Watson AMD, Lambert GW, Smith KJ, May CN : Urotensin II acts centrally to increase epinephrine and ACTH release and cause potent inotropic and chronotropic actions. Hypertension 2003; 42: 373–379.
Silvestre RA, Egido EM, Hernandez R, et al: Urotensin-II is present in pancreatic extracts and inhibits insulin release in the perfused rat pancreas. Eur J Endocrinol 2004; 151: 803–809.
Sheridan MA, Plisetskaya EM, Bern HA, Gorbman A : Effects of somatostatin-25 and urotensin II on lipid and carbohydrate metabolism of coho salmon, Oncorhynchus kisutch. Gen Comp Endocrinol 1987; 66: 405–414.
Douglas SA, Ohlstein EH : Human urotensin-II, the most potent mammalian vasoconstrictor identified to date, as a therapeutic target for the management of cardiovascular disease. Trends Cardiovasc Med 2000; 10: 229–237.
Russell FD, Kearns P, Toth I, Molenaar P : Urotensin-II–converting enzyme activity of furin and trypsin in human cells in vitro. J Pharmacol Exp Ther 2004; 310: 209–214.
Douglas SA, Ohlstein EH : Urotensin receptors, in Girdalstone D ( ed): The IUPHAR Compendium of Receptor Characterization and Classification. London, IUPHAR Media, 2000, pp 365–372.
Protopopov A, Kashuba V, Podowski R, et al: Assignment of the GPR14 gene coding for the G-protein–coupled receptor 14 to human chromosome 17q25.3 by fluorescent in situ hybridization. Cytogenet Cell Genet 2000; 88: 312–313.
Maguire JJ, Davenport AP : Is urotensin-II the new endothelin? Br J Pharmacol 2002; 137: 579–588.
Maguire JJ, Kuc RE, Wiley KE, Kleinz MJ, Davenport AP : Cellular distribution of immunoreactive urotensin-II in human tissues with evidence of increased expression in atherosclerosis and a greater constrictor response of small compared to large coronary arteries. Peptides 2004; 25: 1767–1774.
Bousette N, Patel L, Douglas SA, Ohlstein EH, Giaid A : Increased expression of urotensin II and its cognate receptor GPR14 in atherosclerotic lesions of the human aorta. Atherosclerosis 2004; 176: 117–123.
Richards AM, Charles C : Urotensin II in the cardiovascular system. Peptides 2004; 25: 1795–1802.
Russell FD, Meyers D, Galbraith AJ, et al: Elevated plasma levels of human urotensin-II immunoreactivity in congestive heart failure. Am J Physiol Heart Circ Physiol 2003; 285: 1576–1581.
Johns DG, Ao Z, Naselsky D, et al: Urotensin-II–mediated cardiomyocyte hypertrophy: effect of receptor antagonism and role of inflammatory mediators. Naunyn Schmiedebergs Arch Pharmacol 2004; 370: 238–250.
Birker-Robaczewska M, Boukhadra C, Studer R, Mueller C, Binkert C, Nayler O : The expression of urotensin II receptor (U2R) is up-regulated by interferon-γ. J Recept Signal Transduct Res 2003; 23: 289–305.
Douglas SA, Tayara L, Ohlstein EH, Halawa N, Giaid A : Congestive heart failure and expression of myocardial urotensin II. Lancet 2002; 359: 1990–1997.
Mallamaci F, Cutrupi S, Pizzini P, Tripepi G, Zoccali C : Urotensin II in end-stage renal disease: an inverse correlate of sympathetic function and cardiac natriuretic peptides. J Nephrol 2005; 18: 727–732.
Charles CJ, Rademaker MT, Richards AM, Yandle TG : Urotensin II: evidence for cardiac, hepatic and renal production. Peptides 2005; 26: 2211–2214.
Heringlake M, Kox T, Uzun O, et al: The relationship between urotensin II plasma immunoreactivity and left ventricular filling pressures in coronary artery disease. Regul Pept 2004; 121: 129–136.
Lapp H, Boerrigter G, Costello-Boerrigter LC, et al: Elevated plasma human urotensin-II–like immunoreactivity in ischemic cardiomyopathy. Int J Cardiol 2004; 94: 93–97.
Ng LL, Loke I, O'Brien RJ, Squire IB, Davies JE : Plasma urotensin in human systolic heart failure. Circulation 2002; 106: 2877–2880.
Totsune K, Takahashi K, Arihara Z, et al: Role of urotensin II in patients on dialysis. Lancet 2001; 358: 810–811.
Heller J, Schepke M, Neef M, Woitas R, Rabe C, Sauerbruch T : Increased urotensin II plasma levels in patients with cirrhosis and portal hypertension. J Hepatol 2002; 37: 767–772.
Balat O, Aksoy F, Kutlar I, et al: Increased plasma levels of Urotensin-II in preeclampsia-eclampsia: a new mediator in pathogenesis? Eur J Obstet Gynecol Reprod Biol 2005; 120: 33–38.
Gruson D, Rousseau MF, Ahn SA, van Linden, Ketelslegers JM : Circulating urotensin II levels in moderate to severe congestive heart failure: its relations with myocardial function and well established neurohormonal markers. Peptide 2006, in press.
Gibson A : Complex effects on Gillichthys urotensin II on rat aortic strips. Br J Pharmacol 1987; 91: 205–212.
Ishihata A, Ogaki T, Aita T, Katano Y : Role of prostaglandins in urotensin II–induced vasodilatation in the coronary arteries of aged rats. Eur J Pharmacol 2005; 523: 119–126.
Bottrill FE, Douglas SA, Hiley CR, White R : Human urotensin-II is an endothelium-dependent vasodilator in rat small arteries. Br J Pharmacol 2000; 130: 1865–1870.
Douglas SA, Sulpizio AC, Piercy V, et al: Differential vasoconstrictor activity of human urotensin-II in vascular tissue isolated from the rat, mouse, dog, pig, marmoset and cynomolgus monkey. Br J Pharmacol 2000; 131: 1262–1274.
Maguire JJ, Kuc RE, Davenport AP : Orphan-receptor ligand human urotensin II: receptor localization in human tissues and comparison of vasoconstrictor responses with endothelin-1. Br J Pharmacol 2000; 131: 441–446.
Behm DJ, Harrison SM, Douglas SA, et al: Deletion of the UT receptor gene results in the selective loss of urotensin-II contractile activity in aortae isolated from UT receptor knockout mice. Br J Pharmacol 2003; 139: 464–472.
Russell FD, Molenaar P, O'Brien DM : Cardiostimulant effects of urotensin-II in human heart in vitro. Br J Pharmacol 2001; 132: 5–9.
Bennett RT, Jones RD, Morice AH, Smith CFC, Cowen ME : Vasoconstrictive effects of endothelin-1, endothelin-3, and urotensin II in isolated perfused human lungs and isolated human pulmonary arteries. Thorax 2004; 59: 401–407.
Hillier C, Berry C, Petrie MC, et al: Effects of urotensin II in human arteries and veins of varying caliber. Circulation 2001; 103: 1378–1381.
Stirrat A, Gallagher M, Douglas SA, et al: Potent vasodilator responses to human urotensin-II in human pulmonary and abdominal resistance arteries. Am J Physiol Heart Circ Physiol 2001; 280: H925–H928.
MacLean MR, Alexander D, Douglas SA, et al: Contractile responses to human urotensin-II in rat and human pulmonary arteries: effect of endothelial factors and chronic hypoxia in the rat. Br J Pharmacol 2000; 130: 201–204.
Russell FD : Emerging roles of urotensin-II in cardiovascular disease. Pharmacol Ther 2004; 103: 223–243.
Giebing G, Tolle M, Jurgensen J, et al: Arrestin-independent internalization and recycling of the urotensin receptor contribute to long-lasting urotensin II–mediated vasoconstriction. Circ Res 2005; 97: 707–715.
Opgaard OS, Nothacker HP, Ehlert FJ, Krause DN : Human urotensin II mediates vasoconstriction via an increase in inositol phosphates. Eur J Pharmacol 2000; 406: 265–271.
Tasaki K, Hori M, Ozaki H, Karaki H, Wakabayashi I : Mechanism of human urotensin II–induced contraction in rat aorta. J Pharmacol Sci 2004; 94: 376–383.
Rossowski WJ, Cheng BL, Taylor JE, Datta R, Coy DH : Human urotensin II–induced aorta ring contractions are mediated by protein kinase C, tyrosine kinases and Rho-kinase: inhibition by somatostatin receptor antagonists. Eur J Pharmacol 2002; 438: 159–170.
Sauzeau V, Mellionnec EL, Bertoglio J, Scalbert E, Pacaud P, Loirand G : Human urotensin II–induced contraction and arterial smooth muscle cell proliferation are mediated by RhoA and Rho-kinase. Circ Res 2001; 88: 1102–1104.
Gray GA, Jones MR, Sharif I : Human urotensin II increases coronary perfusion pressure in the isolated rat heart: potentiation by nitric oxide synthase and cyclooxygenase inhibition. Life Sci 2001; 69: 175–180.
Lin L, Ding WH, Jiang W, et al: Urotensin-II activates L-arginine/nitric oxide pathway in isolated rat aortic adventitia. Peptides 2004; 25: 1977–1984.
Bohm F, Pernow J : Urotensin II evokes potent vasoconstriction in humans in vivo. Br J Pharmacol 2002; 135: 25–27.
Wilkinson IB, Affolter JT, de Haas SL, et al: High plasma concentrations of human urotensin II do not alter local or systemic hemodynamics in man. Cardiovasc Res 2002; 53: 341–347.
Affolter JT, Newby DE, Wilkinson IB, Winter MJ, Balment RJ, Webb DJ : No effect on central or peripheral blood pressure of systemic urotensin II infusion in humans. Br J Clin Pharmacol 2002; 54: 617–621.
Sondermeijer B, Kompa A, Komesaroff P, Krum H : Effect of exogenous urotensin-II on vascular tone in skin microcirculation of patients with essential hypertension. Am J Hypertens 2005; 18: 1195–1199.
Behm DJ, Doe CP, Douglas SA, et al: Urotensin-II: a novel systemic hypertensive factor in the cat. Naunyn Schmiedebergs Arch Pharmacol 2004; 369: 274–280.
Lin Y, Tsuchihashi T, Matsumura K, Abe I, Iida M : Central cardiovascular action of urotensin II in conscious rats. J Hypertens 2003; 21: 159–165.
Lin Y, Tsuchihashi T, Matsumura K, et al: Central cardiovascular action of urotensin II in spontaneously hypertensive rats. Hypertens Res 2003; 26: 839–845.
Lu Y, Zou CJ, Huang DW, Tang CS : Cardiovascular effects of urotensin II in different brain areas. Peptides 2002; 23: 1631–1635.
Song W, Ashton N, Balment RJ : A radioimmunoassay to detect urotensin II in the plasma of rat models of hypertension. J Physiol 2002; 544: S024 ( Abstract).
Thompson JP, Watt P, Sanghavi S, Strupish JW, Lambert DG : A comparison of cerebrospinal fluid and plasma urotensin II concentrations in normotensive and hypertensive patients undergoing urological surgery during spinal anesthesia: a pilot study. Anesth Analg 2003; 97: 1501–1503.
Rdzanek A, Filipiak KJ, Karpinski G, Grabowski M, Opolski G : Exercise urotensin II dynamics in myocardial infarction survivors with and without hypertension. Int J Cardiol 2005, in press.
Liu GQ, Zeng ZP, Li HZ, et al: Expression of urotensin II and G-protein coupled receptor 14 mRNA in human pheochromocytoma tissues. Zhongguo Yi Xue Ke Xue Yuan Xue Bao 2005; 27: 457–460.
Yamamoto H, Watanabe T, Miyazaki A, et al: High prevalence of Chlamydia pneumoniae antibodies and increased high-sensitive C-reactive protein in patients with vascular dementia. J Am Geriatr Soc 2005; 53: 583–589.
Rakowski E, Hassan GS, Dhanak D, Ohlstein EH, Douglas SA, Giaid A : A role for urotensin II in restenosis following balloon angioplasty: use of a selective UT receptor blocker. J Moll Cell Cardiol 2005; 39: 785–791.
Wang ZJ, Shi LB, Xiong ZW, et al: Alteration of vascular urotensin II receptor in mice with apolipoprotein E gene knockout. Peptides 2006; 27: 858–863.
Gendron G, Simard B, Gobeil F Jr, Sirois P, D'Orleans-Juste P, Regoli D : Human urotensin-II enhances plasma extravasation in specific vascular districts in Wistar rats. Can J Pysiol Pharmacol 2004; 82: 16–21.
Shi L, Ding W, Li D, et al: Proliferation and anti-apoptotic effects of human urotensin II on human endothelial cells. Atherosclerosis 2005, in press.
Wang H, Mehta JL, Chen K, Zhang X, Li D : Human urotensin II modulates collagen synthesis and the expression of MMP-1 in human endothelial cells. J Cardiovasc Pharmacol 2004; 44: 577–581.
Hongfang J, Bailin C, Bin Z, et al: Effects of hydrogen sulfide on hypoxic pulmonary vascular structural remodeling. Life Sci 2006; 78: 1299–1309.
Dschietzig T, Richter C, Bartsch C, et al: Flow-induced pressure differentially regulates endothelin-1, urotensin II, adrenomedullin, and relaxin in pulmonary vascular endothelium. Biochem Biophys Res Commun 2001; 289: 245–251.
Hori M, Miyazaki A, Tamagawa H, et al: Up-regulation of acyl-coenzyme A:cholesterol acyltransferase-1 by transforming growth factor-β1 during differentiation of human monocytes into macrophages. Biochem Biophys Res Commun 2004; 320: 501–505.
Suguro T, Watanabe T, Miyazaki A, et al: Serotonin acts as an up-regulator of acyl-coenzyme A:cholesterol acyltransferase-1 in human monocyte-macrophages. Atherosclerosis 2005, in press.
Furukawa K, Hori M, Miyazaki A, et al: Adiponectin down-regulates acyl-coenzyme A:cholesterol acyltransferase-1 in cultured human monocyte–derived macrophages. Biochem Biophys Res Commun 2004; 317: 831–836.
Peng X, Yin H, Wang LH, Chai SB, Shu JL, Tang CS : Content and activity of the focal adhesion kinase in cultured vascular smooth muscle cells enhanced by urotensin II. Sheng Li Xue Bao 2000; 52: 455–458.
Djordjevic T, BelAiba RS, Bonello S, Pfeilschifter J, Hess J, Gorlach A : Human urotensin II is a novel activator of NADPH oxidase in human pulmonary artery smooth muscle cells. Arterioscler Thromb Vasc Biol 2005; 25: 519–525.
Tamura K, Okazaki M, Tamura M, Isozumi K, Tasaki H, Nakashima Y : Urotensin II–induced activation of extracellular signal-regulated kinase in cultured vascular smooth muscle cells: involvement of cell adhesion–mediated integrin signaling. Life Sci 2003; 72: 1049–1060.
Shoji M, Yasujima M, Suda T : Effects of urotensin II on platelets. Nippon Rinsho 2004; 62 ( Suppl 9): 715–718 ( in Japanese).
Fang SH, Li ZL, Wu HC, et al: Clinical study of plasma urotensin II in patients with coronary heart disease. Di Yi Jun Yi Da Xue Xue Bao 2004; 24: 563–565.
Hassan GS, Douglas SA, Ohlstein EH, Giaid A : Expression of urotensin-II in human coronary atherosclerosis. Peptides 2005; 26: 2464–2472.
Katugampola SD, Kuc RE, Maguire JJ, Davenport : G-protein–coupled receptors in human atherosclerosis: comparison of vasoconstrictors (endothelin and thromboxane) with recently de-orphanized (urotensin-II, apelin and ghrelin) receptors. Clin Sci (Lond) 2002; 103: 171S–175S.
Paysant J, Rupin A, Simonet S, Fabiani JN, Verbeuren TJ : Comparison of the contractile responses of human coronary bypass grafts and monkey arteries to human urotensin-II. Fundam Clin Pharmacol 2001; 15: 227–231.
Zhou P, Wu SY, Yu CF, et al: Effects of urotensin II on isolated rat hearts under normal perfusion and ischemia reperfusion. Acta Physiol Sin 2003; 55: 442–448.
Tzanidis A, Hannan RD, Thomas WG, et al: Direct actions of urotensin II on the heart: implications for cardiac fibrosis and hypertrophy. Circ Res 2003; 93: 246–253.
Zou Y, Nagai R, Yamazaki T : Urotensin II induces hypertrophic responses in cultured cardiomyocytes from neonatal rats. FEBS Lett 2001; 508: 57–60.
Joyal D, Huynh T, Aiyar N, Guida B, Douglas S, Giaid A : Urotensin-II levels in acute coronary syndromes. Int J Cardiol 2006; 108: 31–35.
Douglas SA : Human urotensin-II as a novel cardiovascular target: ‘heart’ of the matter or simply a fishy ‘tail’? Curr Opin Pharmacol 2003; 3: 159–167.
Herold CL, Behm DJ, Buckley PT, Foley JJ, Douglas SA : The peptidic somatostatin analogs lanreotide, BIM-23127 and BIM-23042 are urotensin-II receptor ligands. Pharmacologist 2002; 44: 170–171.
Clozel M, Binkert C, Birker-Robaczewska M, et al: Pharmacology of the urotensin-II receptor antagonist Palosuran (ACT-058362; 1-[2-(4-benzyl-4-hydroxy-piperidin-1-yl)-ethyl]-3-(2-methyl-quinolin-4-yl)-urea sulfate salt): first demonstration of a pathophysiological role of the urotensin system. J Pharmacol Exp Ther 2004; 311: 204–212.
Clozel M, Hess P, Qiu C, Ding SS, Rey M : The urotensin-II receptor antagonist palosuran improves pancreatic and renal function in diabetic rats. J Pharmacol Exp Ther 2006; 316: 1115–1121.
Patacchini R, Santicioli P, Giuliani S, et al: Urantide: an ultrapotent urotensin II antagonist peptide in the rat aorta. Br J Pharmacol 2003; 140: 1155–1158.
Dhanak D, Neeb MJ, Douglas SA : Urotensin-II receptor modulators. Annu Rep Med Chem 2003; 38: 99–110.
Bousette N, Ohlstein EH, Dhanak D, Douglas SA, Giaid A : Urotensin-II receptor blockade reduces mortality and improves congestive heart failure. Circulation 2005; 112: II-453.
Gardiner SM, March JE, Kemp PA, Bennett : Bolus injection of human UII in conscious rats evokes a biphasic haemodynamic response. Br J Pharmacol 2004; 143: 422–430.
Gendron G, Gobeil F Jr, Belanger S, Gagnon S, Regoli D, D'Orleans-Juste P : Urotensin II–induced hypotensive responses in Wistar-Kyoto (Wky) and spontaneously hypertensive (Shr) rats. Peptide 2005; 26: 1468–1474.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Watanabe, T., Kanome, T., Miyazaki, A. et al. Human Urotensin II as a Link between Hypertension and Coronary Artery Disease. Hypertens Res 29, 375–387 (2006). https://doi.org/10.1291/hypres.29.375
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1291/hypres.29.375
Keywords
This article is cited by
-
The relationship between urotensin II and insulin resistance in women with gestational diabetes mellitus
Hormones (2019)
-
Genome-Wide Linkage Analysis of Large Multiple Multigenerational Families Identifies Novel Genetic Loci for Coronary Artery Disease
Scientific Reports (2017)
-
Is the serum level of salusin-β associated with hypertension and atherosclerosis in the pediatric population?
Pediatric Nephrology (2015)
-
Increased TRPC3 expression in vascular endothelium of patients with malignant hypertension
Modern Pathology (2009)
-
Urotensin II acutely increases myocardial length and distensibility: potential implications for diastolic function and ventricular remodeling
Naunyn-Schmiedeberg's Archives of Pharmacology (2007)