Potential clinical implications of the urotensin II receptor antagonists

Frontiers in Pharmacology

Volumn JUL, Issue , 2011, Pages

  Tsoukas, Philip ^a   Kane, Émilie ^a   Giaid, Adel ^a  

^a MONTREAL GENERAL HOSPITAL   (Canada)

Author keywords

Antagonist; Heart; Kidney; Metabolic syndrome; Ut

Indexed keywords

2,6 DICHLORO N [4 CHLORO 3 [2 (DIMETHYLAMINO)ETHOXY]PHENYL] 4 (TRIFLUOROMETHYL)BENZENESULFONAMIDE; ACETYL LOW DENSITY LIPOPROTEIN; ACYL COENZYME A:CHOLESTEROL ACYLTRANSFERASE 1; ANGIOTENSIN RECEPTOR ANTAGONIST; BIM 23127; CHOLESTEROL ACYLTRANSFERASE; DIPEPTIDYL CARBOXYPEPTIDASE INHIBITOR; ET 1; PALOSURAN; PIPERAZINOISOINDOLINONE BASED ANTAGONIST; UNCLASSIFIED DRUG; URANTIDE; UROTENSIN II; UROTENSIN RECEPTOR; UROTENSIN RECEPTOR ANTAGONIST; VASOCONSTRICTOR AGENT;

ACUTE KIDNEY FAILURE; ALBUMINURIA; ANTIINFLAMMATORY ACTIVITY; ARTERY INTIMA PROLIFERATION; ARTICLE; BINDING AFFINITY; CHRONIC KIDNEY FAILURE; COMPETITIVE INHIBITION; CONGESTIVE HEART FAILURE; CORONARY ARTERY ATHEROSCLEROSIS; DIABETIC NEPHROPATHY; DRUG BIOAVAILABILITY; DRUG BLOOD LEVEL; DRUG POTENCY; DRUG POTENTIATION; DRUG PROTEIN BINDING; ENZYME ACTIVITY; ENZYME INHIBITION; ESSENTIAL HYPERTENSION; HEART DISEASE; HEART MUSCLE FIBROSIS; HEART VENTRICLE HYPERTROPHY; HUMAN; HYPERTENSION; INSULIN DEPENDENT DIABETES MELLITUS; KIDNEY DISEASE; KIDNEY TUBULE DISORDER; LUNG EDEMA; MAXIMUM PLASMA CONCENTRATION; METABOLIC SYNDROME X; MICROALBUMINURIA; NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; PATHOPHYSIOLOGY; PROPHYLAXIS; PROTEIN BLOOD LEVEL; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN SECRETION; RESTENOSIS; UNSPECIFIED SIDE EFFECT; UPREGULATION; VASOCONSTRICTION; VASODILATATION;

EID: 84857955289     PISSN: None     EISSN: 16639812     Source Type: Journal    
DOI: 10.3389/fphar.2011.00038     Document Type: Article

References (114)

1. Albertin, G., Casale, V., Ziolkowska, A., Spinazzi, R., Malendowicz, L. K., Rossi, G. P., and Nussdorfer, G. G. (2006). Urotensin-II and UIIreceptor expression and function in the rat adrenal cortex. Int. J. Mol. Med. 17, 1111-1115.
2. Ames, R. S., Sarau, H. M., Chambers, J. K., Willette, R. N., Aiyar, N. V., Romanic, A. M., Louden, C. S., Foley, J. J., Sauermelch, C. F., Coatney, R. W., Ao, Z., Disa, J., and Holmes, S. D., Stadel, J. M., Martin, J. D., Liu, W. S., Glover, G. I., Wilson, S., McNulty, D. E., Ellis, C. E., Elshourbagy, N. A., Shabon, U., Trill, J. J., Hay, D. W., Ohlstein, E. H., Bergsma, D. J., and Douglas, S. A. (1999). Human urotensin-II is a potent vasoconstrictor and agonist for the orphan receptor GPR14. Nature 401, 282-286.
3. Ashton, N. (2006). Renal and vascular actions of urotensin II. Kidney Int. 70, 624-629.
4. Balat, O., Aksoy, F., Kutlar, I., Ugur, M., Iyikosker, H., Balat, A., and Anarat, R. (2005). Increased plasma levels of urotensin-II in preeclampsiaeclampsia: a new mediator in pathogenesis? Eur. J. Obstet. Gynecol. Reprod. Biol. 120, 33-38.
5. Behm, D. J., Herold, C. L., Ohlstein, E. H., Knight, S. D., Dhanak, D., and Douglas, S. A. (2002). Pharmacological characterization of SB-710411(Cpa-c[D-Cys-Pal-D-Trp-Lys-Val-Cys]-Cpa-amide), a novel peptidic urotensin-II receptor antagonist. Br. J. Pharmacol. 137, 449-458.
6. Behm, D. J., McAtee, J. J., Dodson, J. W., Neeb, M. J., Fries, H. E., Evans, C. A., Hernandez, R. R., Hoffman, K. D., Harrison, S. M., Lai, J. M., Wu, C., Aiyar, N. V., Ohlstein, E. H., and Douglas, S. A. (2008). Palosuran inhibits binding to primate UT receptors in cell membranes but demonstrates differential activity in intact cells and vascular tissues. Br. J. Pharmacol. 155, 374-386.
7. Bergman, R. N., and Ader, M. (2000). Free fatty acids and pathogenesis of type 2 diabetes mellitus. Trends Endocrinol. Metab. 11, 351-356.
8. Bohm, F., and Pernow, J. (2002). Urotensin II evokes potent vasoconstriction in humans in vivo. Br. J. Pharmacol. 135, 25-27.
9. Bottrill, F. E., Douglas, S. A., Hiley, C. R., and White, R. (2000). Human urotensin-II is an endotheliumdependent vasodilator in rat small arteries. Br. J. Pharmacol. 130, 1865-1870.
10. Bousette, N., D'Orleans-Juste, P., Kiss, R. S., You, Z., Genest, J., Al-Ramli, W., Qureshi, S. T., Gramolini, A., Behm, D., Ohlstein, E. H., Harrison, S. M., Douglas, S. A., and Giaid, A. (2009). Urotensin II receptor knockout mice on anApoE knockout background fed a high-fat diet exhibit an enhanced hyperlipidemic and atherosclerotic phenotype. Circ. Res. 105, 686-695.
11. Bousette, N., Hu, F., Ohlstein, E. H., Dhanak, D., Douglas, S. A., and Giaid, A. (2006a). Urotensin-II blockade with SB-611812 attenuates cardiac dysfunction in a rat model of coronary artery ligation. J. Mol. Cell. Cardiol. 41, 285-295.
12. Bousette, N., Pottinger, J., Ramli, W., Ohlstein, E. H., Dhanak, D., Douglas, S. A., and Giaid, A. (2006b). Urotensin-II receptor blockade with SB-611812 attenuates cardiac remodeling in experimental ischemic heart disease. Peptides 27, 2211-2214.
13. Bousette, N., Patel, L., Douglas, S. A., Ohlstein, E. H., and Giaid,A. (2004). Increased expression of urotensin II and its cognate receptor GPR14 in atherosclerotic lesions of the human aorta. Atherosclerosis 176, 117-123.
14. Brantsma, A. H., Baker, S. J., de Zeeuw, D., de Jong, P. E., and Gansevoort, R. T. (2006). Urinary albumin excretion as a predictor of the development of hypertension in the general population. J. Am. Soc. Nephrol. 17, 331-335.
15. Camarda, V., Rizzi, A., Calò, G., Gendron, G., Perron, S. I., Kostenis, E., Zamboni, P., Mascoli, F., and Regoli, D. (2002). Effects of human urotensin II in isolated vessels of various species; comparison with other vasoactive agents. Naunyn Schmiedebergs Arch. Pharmacol. 365, 141-149.
16. Camarda, V., Song, W., Marzola, E., Spagnol, M., Guerrini, R., Salvadori, S., Regoli, D., Thompson, J. P., Rowbotham, D. J., Behm, D. J., Douglas, S. A., Calo', G., and Lambert, D. G. (2004). Urantide mimics urotensin-II induced calcium release in cells expressing recombinant UT receptors. Eur. J. Pharmacol. 498, 83-86.
17. Cheung, B. M. Y., Leung, R., Man, Y. B., and Wong, L. Y. (2004). Plasma concentration of urotensin II is raised in hypertension. J. Hypertens. 22, 1341-1344.
18. Clozel, M., Binkert, C., BirkerRobaczewska, M., Boukhadra, C., Ding, S.-S., Fischli, W., Hess, P., Mathys, B., Morrison, K., Müller, C., Müller, C., Nayler, O., Qiu, C., Rey, M., Scherz, M. W., Velker, J., Weller, T., Xi, J. F., and Ziltener, P. (2004). Pharmacology of the urotensin-II receptor antagonist palosuran (ACT058362; 1-[2-(-benzyl-4-hydroxypiperidin-1-yl)-ethyl]-3-(2-methylquinolin-4-yl)-urea sulphate salt): first demonstration of a pathophysiological role of the urotensin system. J. Pharmacol. Exp. Ther. 311, 204-212.
19. Clozel, M., Hess, P., Qui, C., Ding, S. S., and Rey, M. (2006). The urotensinII receptor antagonist palosuran improves pancreatic and renal function in diabetic rats. J. Pharmacol. Exp. Ther. 316, 1115-1121.
20. Colton, J. M., Yano, K., Waugh, D., and Hazon, N. (1996). Distribution and molecular forms of urotensin II and its role in cardiovascular regulation in vertebrates. J. Exp. Zool. 275, 226-238.
21. Dai, H. Y., Kang, W. Q., Wang, X., Yu, X. J., Li, Z. H., Tang, M. X., Xu, D. L., Li, C. W., Zhang, Y., and Ge, Z. M. (2007). The involvement of transforming growth factor-beta1 secretion in urotensin II-induced collagen synthesis in neonatal cardiac fibroblasts. Regul. Pept. 140, 88-93.
22. de Zeeuw, D. (2004). Should albuminuria be a therapeutic target in patients with hypertension and diabetes? Am.J.Hypertens. 17, 11S-15S.
23. DeFronzo, R. A., Tobin, J. D., and Andres, R. (1979). Glucose clamp technique: a method for quantifying insulin secretion and resistance. Am. J. Physiol. 237, E214-E223.
24. Desai, N., Sajjad, J., and Frishman, W. H. (2008). Urotensin II: a new pharmacologic target in the treatment of cardiovascular disease. Cardiol. Rev. 16, 142-153.
25. Disa, J., Floyd, L. E., Edwards, R. M., Douglas, S. A., and Aiyar, N. V. (2005). Identification and characterization of binding sites for human urotensin-II in Sprague-Dawley rat renal medulla using quantitative receptor autoradiography. Peptides 27, 1532-1537.
26. Djordjevic, T., BelAiba, R. S., Bonello, S., Pfeilschifter, J., Hess, J., and Görlach, A. (2005). Human urotensin II is a novel activator of NADPH oxidase in human pulmonary artery smooth muscle cells. Arterioscler. Thromb. Vasc. Biol. 25, 519-525.
27. Douglas, S. A. (2003). Human urotensin-II as a novel cardiovascular target: "heart" of the matter or simply a fishy "tail"? Curr. Opin. Pharmacol. 3, 159-167.
28. Douglas, S. A., Sulpizio, A. C., Piercy, V., Sarau, H. M., Ames, R. S., Aiyar, N. V., Ohlstein, E. H., and Willette, R. N. (2000). Differential vasoconstrictor activity of human urotensin-II in vascular tissue isolated from the rat, mouse, dog, pig, marmoset and cynomolgus monkey. Br. J. Pharmacol. 131, 1262-1274.
29. Douglas, S. A., Dhanak, D., and Johns, D. G. (2004a). From "gills to pills": urotensin-II as a regulator of mammalian cardiorenal function. Trends Pharmacol. Sci. 25, 76-85.
30. Douglas, S. A., Naselsky, D., Ao, Z., Disa, J., Herold, C. L., Lynch, F., and Aiyar, N. V. (2004b). Identification and pharmacological characterization of native, functional human urotensinII receptors in rhabdomyosarcoma cell lines. Br. J. Pharmacol. 142, 921-932.
31. Douglas, S. A., and Ohlstein, E. H. (2000). Human urotensin-II, the most potent mammalian vasoconstrictor identified to date, as a therapeutic target for the management of cardiovascular disease. Trends Cardiovasc. Med. 131, 1262-1274.
32. Douglas, S. A., Tayara, L., Ohlstein, E. H., Halawa, N., and Giaid, A. (2002). Congestive heart failure and expression of myocardial urotensin II. Lancet 359, 1990-1997.
33. Elahi, D. (1996). In praise of the hyperglycaemic clamp. A method for assessment of beta-cell sensitivity and insulin resistance. Diabetes Care 19, 278-286.
34. El-Atat, F. A., Stas, S. N., McFarlane, S. I., and Sowers, J. R. (2004). The relationship between hyperinsulinemia, hypertension and progressive renal disease. J. Am. Soc. Nephrol. 15, 2816-2827.
35. Elshourbagy, N. A., Douglas, S. A., Shabon, U., Harrison, S., Duddy, G., Sechler, J. L., Ao, Z., Maleeff, B. E., Naselsky, D., Disa, J., and Aiyar, N. V. (2002). Molecular and pharmacological characterization of genes encoding urotensin-II peptides and their cognate G-proteincoupled receptors from the mouse and monkey. Br. J. Pharmacol. 136, 9-22.
36. Fernandez-Real, J. M., and Ricart, W. (2003). Insulin resistance and chronic cardiovascular inflammatory syndrome. Endocr. Rev. 24, 278-301.
37. Gardiner, S. M., March, J. E., Kemp, P. A., Maguire, J. J., Kuc, R. E., Davenport, A. P., and Bennett, T. (2006). Regional heterogeneity in the haemodynamic responses to urotensin II infusion in relation to UT receptor localisation. Br. J. Pharmacol. 147, 612-621.
38. Gibson, A. (1987). Complex effects of Gillichthys urotensin II on rat aortic strips. Br. J. Pharmacol. 91, 205-212.
39. Gray, G. A., Jones, M. R., and Sharif, I. (2001). Human urotensin II increases coronary perfusion pressure in the isolated rat heart. Potentiation by nitric oxide synthase and cyclooxygenase inhibition.LifeSci. 69, 175-180.
40. Grundy, S. M., Cleeman, J. I., and Daniels, S. R. (2005). Diagnosis and management of the metabolic syndrome: an American Heart Association/National Heart, Lung, and Blood Institute scientific statement. Circulation 112, 2735-2752.
41. Gruson, D., Rousseau, M. F., Ahn, S. A., van Linden, F., and Ketelslegers, J. M. (2006). Circulating urotensin II levels in moderate to severe congestive heart failure: its relations with myocardial function and well established neurohormonal markers. Peptides 27, 1527-1531.
42. Hassan, G. S., Chouiali, F., Saito, T., Hu, F., Douglas, S. A., Ao, Z., Willette, R. N., Ohlstein, E. H., and Giaid, A. (2003). Effect of human urotensin-II infusion on hemodynamics and cardiac function. Can. J. Physiol. Pharmacol. 81, 125-128.
43. Hassan, G. S., Douglas, S. A., Ohlstein, E. H, and Giaid, A. (2005). Expression of urotensin-II in human coronary atherosclerosis. Peptides 26, 2462-2472.
44. Heller, J., Schepke, M., Neef, M., Woitas,R.,Rabe,C.,and Sauerbruch, T. (2002). Increased urotensin II plasma levels in patients with cirrhosis and portal hypertension. J. Hepatol. 37, 767-772.
45. Herold, C. L., Behm, D. J., Buckley, P. T., Foley, J. J., Wixted, W. E., Sarau, H. M., and Douglas, S. A. (2003). The neuromedin B receptor antagonist, BIM-23127, is a potent antagonist at human and rat urotensinII receptors. Br. J. Pharmacol. 139, 203-207.
46. Hunt, S. A., Baker, D. W., Chin, M. H., Cinquegrani, M. P., Feldman, A. M., Francis, G. S., Ganiats, T. G., Goldstein, S., Gregoratos, G., Jessup, M. L., Noble, R. J., Packer, M., Silver, M. A., Stevenson, L. W., Gibbons, R. J., Antman,E. M.,Alpert,J. S.,Faxon,D. P., Fuster, V., Gregoratos, G., Jacobs, A. K., Hiratzka, L. F., Russell, R. O., Smith, S. C. Jr., and American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Revise the 1995 Guidelines for the Evaluation and Management of Heart Failure), International Society for Heart and Lung Transplantation, Heart Failure Society of America. (2001). ACC/AHA Guidelines for the evaluation and management of chronic heart failure in the adult: executive summary. Circulation 104, 2996-3007.
47. IDF Epidemiology Task Force Consensus Group. (2005). The metabolic syndrome-anewworldwidedefinition. Lancet 366, 1059-1062.
48. Ishihata, A., Ogaki, T., Aita, T., and Katano, Y. (2005). Role of prostaglandins in urotensin IIinduced vasodilation in the coronary arteries of aged rats. Eur. J. Pharmacol. 523, 119-126.
49. Ishihata, A., Sakai, M., and Katano, Y. (2006). Vascular contractile effect of urotensin II in young and aged rats: influence of aging and contribution of endothelial nitric oxide. Peptides 27, 80-86.
50. Johns,D. G.,Ao,Z.,Naselsky,D.,Herold, C. L., Maniscalco, K., Sarov-Blat, L., Steplewski, K., Aiyar, N., and Douglas, S. A. (2004). UrotensinII-mediated cardiomyocyte hypertrophy: effect of receptor antagonism and role of inflammatory mediators. Arch. Pharmacol. 370, 238-250.
51. Katano, Y., Ishihata, A., Aita, T., Ogaki, T., and Horie, T. (2000). Vasodilator effect of urotensin II, one of the most potent vasoconstricting factors, on rat coronary arteries. Eur. J. Pharmacol. 402, 209-211.
52. Khan, S. Q., Bhandari, S. S., Quinn, P., Davies, J. E., and Ng, L. L. (2007). Urotensin II is raised in acute myocardial infarction and low levels predict risk of adverse clinical outcome in humans. Int. J. Cardiol. 117, 323-327.
53. Lach, E. B., Broad, S., and Rozengurt, E. (1995). Mitogenic signalling by transfected neuromedin B receptors in Rat-1 cells. Cell Growth Differ. 6, 1427-1435.
54. Lacza, Z., and Busija, D. W. (2006). Urotensin-II is a nitric oxidedependent vasodilator in the pial arteries of the newborn pig. Life Sci. 78, 2763-2766.
55. Lane, J. T. (2004). Microalbuminuria as a marker of cardiovascular and renal risk in type 2 diabetes mellitus: a temporal perspective. Am. J. Physiol. Renal Physiol. 286, F442-F450.
56. Langham, R. G., Kelly, D. J., Gow, R. M., Zhang, Y., Dowling, J. K., Thomson, N. M., and Gilbert, R. E. (2004). Increased expression of urotensin II and urotensin II receptor in human diabetic nephropathy. Am. J. Kidney Dis. 44, 826-831.
57. Lapp, H., Boerrigter, G., CostelloBoerrigter, L. C., Jaekel, K., Scheffold, T., Krakau, I., Schramm, M., Guelker, H., and Stasch, J. P. (2004). Elevated plasma human urotensinII-like immunoreactivity in ischemic cardiomyopathy. Int. J. Cardiol. 94, 93-97.
58. Lawson, E. D., Luci, D. K., Ghosh, S., Kinney,W. A., Reynolds, C. H., Qi, J., Smith, C. E., Wang, Y., Minor, L. K., Haertlein, B. J., Parry, T. J., Damiano, B. P., and Maryanoff, B. E. (2009). Nonpeptide urotensin-II receptor antagonists: a new ligand class based on piperazino-phthalimide and piperazino-isoindolinone subunits. J. Med. Chem. 52, 7432-7445.
59. Li, L., Yuan, W. J., and Su, D. F. (2004). Effects of rat urotensin II on coronary flow and myocardial eNOS protein expression in isolated rat heart. Acta Pharmacol. Sin. 25, 1444-1449.
60. Lim, M., Honisett, S., Sparkes, C. D., Komesaroff, P., Kompa, A., and Krum, H. (2004). Differential effect of urotensin II on vascular tone in normal subjects and patients with chronic heart failure. Circulation 109, 1212-1214.
61. Liu, Q., Pong, S. S., Zeng, Z., Zhang, Q., Howard, A. D., Williams, D. L. Jr., Davidoff, M., Wang, R., Austin, C. P., McDonald, T. P., Bai, C., George, S. R., Evans, J. F., and Caskey, C. T. (1999). Identification of urotensin II as the endogenous ligand for the orphan G-protein-coupled receptor GPR14. Biochem. Biophys. Res. Commun. 266, 174-178.
62. MacLean, M. R., Alexander, D., Stirrat, A., Gallagher, M., Douglas, S. A., Ohlstein, E. H., Morecroft, I., and Polland, K. (2000). 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. 130, 201-204.
63. Maguire, J. J., Kuc, R. E., and Davenport, A. P. (2000). Orphan-receptor ligand human urotensin II: receptor localization in human tissues and comparison of vasoconstrictor responses with endothelin-1. Br. J. Pharmacol. 131, 441-446.
64. Maguire, J. J., Kuc, R. E., Wiley, K. E., Kleinz, M. J., and Davenport, A. P. (2004). Cellular distribution of immunoreactive urotensinII in human tissues with evidence of increased expression in atherosclerosis and a greater constrictor response of small compared to large coronary arteries. Peptides 25, 1767-1774.
65. Malagon, M. M., Molina, M., Gahete, M. D., Duran-Prado, M., MartinezFuentes, A. J., Alcain, F. J., Tonon, M. C., Leprince, J., Vaudry, H., Castaño, J. P., and Vazquez-Martinez, R. (2008). Urotensin II and urotensin II-related peptide activate somatostatin receptor subtypes 2 and 5. Peptides 29, 711-720.
66. Mallamaci, F., Cutrupi, S., Pizzini, P., Tripepi, G., and Zoccali, C. (2005). Urotensin II in end-stage renal disease: an inverse correlate of sympathetic function and cardiac natriuretic peptides. J. Nephrol. 18, 727-732.
67. Matsushita, M., Shichiri, M., Imai, T., Iwashina, M., Tanaka, H., Takasu, N., and Hirata,Y. (2001). Co-expression of urotensin II and its receptor (GPR14) in human cardiovascular and renal tissues. J. Hypertens. 19, 2185-2190.
68. Ng, L. L., Loke, I., O'Brien, R. J., Squire, I. B., and Davies, J. E. (2002). Plasma urotensin in human systolic heart failure. Circulation 106, 2877-2880.
69. Onan, D., Pipolo, L., Yang, E., Hannan, R. D., and Thomas, W. G. (2004). Urotensin II promotes hypertrophy of cardiac myocytes via mitogen-activated protein kinases. Mol. Endocrinol. 18, 2344-2354.
70. Ovcharenko, E., Abassi, Z., Rubinstein, I., Kaballa, A., Hoffman, A., and Winaver, J. (2006). Renal effects of human urotensin-II in rats with experimental congestive heart failure. Nephrol. Dial. Transplant. 21, 1205-1211.
71. Pakala, R. (2007). Role of urotensin II in atherosclerotic cardiovascular diseases. Cardiovasc. Revasc. Med. 9, 166-178.
72. Patacchini, R., Santicioli, P., Giuliani, S., Grieco, P., Novellino, E., Rovero, P., and Maggi, C. A. (2003). Urantide: an ultrapotent urotensin II antagonist peptide in rat aorta. Br. J. Pharmacol. 140, 1155-1158.
73. Rajala, M. W., and Scherer, P. E. (2003). The adipocyte - at the crossroads of energy homeostasis, inflammation, and atherosclerosis. Endocrinology 144, 3765-3673.
74. Rakowski, E., Hassan, G. S., Dhanak, D., Ohlstein, E. H., Douglas, S. A., and Giaid, A. (2005). A role for urotensin II in restenosis following balloon angioplasty: use of a selective UT receptor blocker. J. Mol. Cell. Cardiol. 39, 785-791.
75. Richards,A. M.,Nicholls,M. G.,Lainchbury, J. G., Fisher, S., and Yandle, T. G. (2002). Plasma urotensin II in heart failure. Lancet 360, 545-546.
76. Russell, F. D. (2008). Urotensin II in cardiovascular regulation. Vasc. Health Manag. 4, 775-785.
77. Russell, F. D., Meyers, D., Galbraith, A. J., Bett, N., Toth, I., Kearns, P., and Molenaar, P. (2003). Elevated plasma levels of human urotensin-II immunoreactivity in congestive heart failure. Am. J. Physiol. Heart Circ. Physiol. 285, H1576-H1581.
78. Russell, F. D., and Molenaar, P. (2004). Investigation of signalling pathways that mediate the inotropic effect of urotensin-II in human heart. Cardiovasc. Res. 63, 673-681.
79. Saltiel, A. R., and Kahn, C. R. (2001). Insulin signalling and the regulation of glucose and lipid metabolism. Nature 414, 799-807.
80. Sano, M., Fukuda, K., Kodama, H., Pan, J., Saito, M., Matsuzaki, J., Takahashi, T., Makino, S., Kato, T., and Ogawa,S. (2000). Interleukin-6 family of cytokines mediate angiotensin II-induced cardiac hypertrophy in rodent cardiomyocytes. J. Biol. Chem. 275, 29717-22923.
81. Sauzeau, V., Le Mellionnec, E., Bertoglio, J., Scalbert, E., Pacaud, P., and Loirand, G. (2001). Human urotensin II-induced contraction and arterial smooth muscle cell proliferation are mediated by RhoA and Rho-kinase. Circ. Res. 88, 1102-1104.
82. Segev, Y., Eshet, R., Rivkis, I., Hayat, C., Kachko, L., Phillip, M., and Landau, D. (2004). Comparison between somatostatin analogues and ACE inhibitor in the NOD mouse model of diabetic kidney disease. Nephrol. Dial. Transplant. 19, 3021-3028.
83. Shenouda, A., Douglas, S. A., Ohlstein, E. H., and Giaid, A. (2002). Localization of urotensin-II immunoreactivity in normal human kidneys and renal carcinoma. J. Histochem. Cytochem. 50, 885-889.
84. Sidharta, P. N., Rave, K., Heinemann, L., Chiossi, E., Krähenbühl, S., and Dingemanse, J. (2009). Effect of the urotensin-II receptor antagonist palosuran on secretion of and sensitivity to insulin in patients with type 2 diabetes mellitus. Br. J. Clin. Pharmacol. 68, 502-510.
85. Sidharta, P. N., Wagner, F. D., Bohnemeier, H., Jungnik, A., Halabi, A., Krähenbühl, S., Chadha-Boreham, H.,and Dingemanse,J. (2006). Pharmacodynamics and pharmacokinetics of the urotensin II receptor antagonist palosuran in macroalbuminuric, diabetic patients. Clin. Pharmacol. Ther. 80, 246-256.
86. Silvestre, R. A., Edigo, E. M., Hernández, R., Leprince, J., Chatenet, D., Tollemer, H., Chartrel, N., Vaudry, H., and Marco, J. (2004). Urotensin-II is present in pancreatic extracts and inhibits insulin release in the perfused rat pancreas. Eur. J. Endocrinol. 151, 803-809.
87. Silvestre, R. A., Rodriguez-Gallardo, J., Egido, E. M., and Marco, J. (2001). Inhibition of insulin release by urotensin II-a study on the perfused rat pancreas. Horm. Metab. Res. 33, 379-381.
88. Simpson, C. M., Penny, D. J., Stocker, C. F., and Shekerdemian, L. S. (2006). Urotensin II is raised in children with congenital heart disease. Heart 92, 983-984.
89. Sondermeijer, B., Komp, A., Komesaroff, P., and Krum, H. (2005). Effects of exogenous urotensin-II on vascular tone in skin microcirculation of patients with essential hypertension. Am.J.Hypertens.22, 1341-1344.
90. Song, W., Abdel-Razik, A. E., Lu, W., Ao, Z., Johns, D. G., Douglas, S. A., Balment, R. J., and Ashton, N. (2006). Urotensin II and renal function in the rat. Kidney Int. 69, 1360-1368.
91. Sowers, J. R. (2004). Insulin resistance and hypertension. Am. J. Physiol. Heart Circ. Physiol. 286, H1597-H1602.
92. Spinazzi, R., Albertin, G., Nico, B., Guidolin, D., Di Liddo, R., Rossi, G. P., Ribatti, D., and Nussdorfer, G. G. (2006). Urotensin-II and its receptor (UT-R) are expressed in rat brain endothelial cells, and urotensin-II via UT-R stimulates angiogenesis in vivo and in vitro. Int. J. Mol. Med. 18, 1107-1112.
93. Strowski, M. Z., Cashen, D. E., Birzin, E. T., Yang, L., Singh, V., Jacks, T. M., Nowak, K. W., Rohrer, S. P., Patchett, A. A., Smith, R. G., and Schaeffer, J. M. (2006). Antidiabetic activity of a highly potent and selective nonpeptide somatostatin receptor subtype-2 agonist. Endocrinology 147, 4664-4673.
94. Suguro,T.,Watanabe,T.,Ban,Y.,Kodate, S., Misaki, A., Hirano, T., Miyazaki, A., and Adachi, M. (2007). Increased human urotensin II levels are correlated with carotid atherosclerosis in essential hypertension. Am. J. Hypertens. 20, 211-217.
95. Suzuki,S.,Wenyi,Z.,Hirai,M.,Hinokio, Y., Suzuki, C.,Yamada, T.,Yoshizumi, S., Suzuki, M., Tanizawa, Y., Matsutani, A., and Oka, Y. (2004). Genetic variations at urotensin II and urotensin II receptor genes and risk of type 2 diabetes mellitus in Japanese. Peptides 25, 1803-1808.
96. Tamura, K., Okazaki, M., Tamura, M., Isozumi, K., Tasaki, H., and Nakashima, Y. (2003). Urotensin II-induced activation of extracellular signal-regulated kinase in cultured vascular smooth muscle cells: involvement of cell adhesionmediated integrin signalling. Life Sci. 72, 1049-1060.
97. Totsune, K., Takahashi, K., Arihara, Z., Sone, M., Ito, S., and Murakami, O. (2003). Increased plasma urotensin II levels in patients with diabetes mellitus. Clin. Sci. 104, 1-5.
98. Totsune, K., Takahashi, K., Arihara, Z., Sone, M., Murakami, O., Ito, S., Kikuya, M., Ohkubo, T., Hashimoto, J., and Imai, Y. (2004). 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 25, 1809-1814.
99. Tölle, M., and van der Giet, M. (2008). Cardiorenovascular effects of urotensin II and relevance of the UT receptor. Peptides 29, 743-763.
100. Totsune, K., Takahashi, K., Arihara, Z., Sone, M., Satoh, F., Ito, S., Kimura, Y., Sasano, H., and Murakami, O. (2001). Role of urotensin II in patients with on dialysis. Lancet 358, 810-811.
101. Tzanidis, A., Hannan, R., Thomas, W., Onan, W., Autelitano, D., See, F., and Krum, H. (2001). Increased expression of urotensin II and its receptor in an experimental model of left ventricular myocardial infarction in the rat: implications for cardiac remodeling. Eur. Heart J. 22, 141.
102. Tzanidis, A., Hannan, R. D., and Thomas, W. G. (2003). Direct actions of urotensin II on the heart implications for cardiac fibrosis and hypertrophy. Circ. Res. 93, 246-253.
103. Wang, D., Iversen, J., Wilcox, C. S., and Strandgaard, S. (2003). Endothelial dysfunction and reduced nitric oxide in resistance arteries in autosomaldominant polycystic kidney disease. Kidney Int. 64, 1381-1388.
104. Watanabe, T., Pakala, R., and Katagiri, T. (2001a). Synergistic effect of urotensin II with mildly oxidized LDL on DNA synthesis in vascular smooth muscle cells. Circulation 104, 16-18.
105. Watanabe, T., Pakala, R., and Katagiri, T. (2001b). Synergistic effect of urotensin II with serotonin on vascular smooth muscle cell proliferation. J. Hypertens. 19, 2191-2196.
106. Watanabe, T., Koba, S., Katagiri, T., Pakala, R., and Benedict, C. R. (2002). Lysophosphatidylcholine potentiates the mitogenic effect of various vasoactive compounds on rabbit aortic smooth muscle cells. Jpn. Heart J. 43, 409-416.
107. Watanabe, T., Suguro, T., Kanome, T., Sakamoto, Y., Kodate, S., Hagiwara, T., Hongo, S., Hirano, T., Adachi, M., and Miyazaki,A. (2005). Human urotensin II accelerates foam cell formation in human monocytederived macrophage. Hypertension 46, 738-744.
108. Wellen, K. E., and Hotamisligil, G. S. (2003). Obesity-induced inflammatory changes in adipose tissue. J. Clin. Invest. 112, 1785-1788.
109. Zhang, A. Y., Chen, Y. -F., Zhang, D. X., Yi, F. X., Qi, J., Andrade-Gordon, P., de Garavilla, L., Li, P. L., and Zou, A. P. (2003). Urotensin II is a nitric oxide-dependent vasodilator and natriuretic peptide in the rat kidney. Am. J. Physiol. Renal Physiol. 385, F792-F798.
110. Zhang, Y., Li, J., Cao, J., Chen, J., Yan, J., Zhang, Z., Du, J., and Tang, C. (2002). Effect of chronic hypoxia on contents of urotensin II and its functional receptors in rat myocardium. Heart Vessels 16, 64-68.
111. Zhou, P., Wu, S. Y., Yu, C. F., Wang, H., Tang, C. S., Lin, L., and Yuan, W. J. (2003). Effects of urotensin II on isolated rat hearts under normal perfusion and ischemia reperfusion. ShengLiXueBao55, 442-448.
112. Zhu, Y.-C., Zhu, Y.-Z., and Moore, P. K. (2006). The role of urotensin II in cardiovascular and renal physiology and diseases. Br. J. Pharmacol. 148, 884-901.
113. Zoccali, C., Mallamaci, F., Tripepi, G., Cutrupi, S., Pizzini, P., and Malatino, L. (2006). Urotensin II is an inverse predictor of incident cardiovascular events in end-stage renal disease. Kidney Int. 69, 1253-1258.
114. Zou, Y., Nagai, R., and Yamazaki, T. (2001). Urotensin II induces hypertrophic responses in cultured cardiomyocytes from neonatal rats. FEBS Lett. 508, 57-60.