Skip to main content

Advertisement

SpringerLink
Log in

Urotensin II: Its Function in Health and Its Role in Disease

  • Review Article
  • Published:
Cardiovascular Drugs and Therapy Aims and scope Submit manuscript

Abstract

Urotensin II (U-II) is the most potent vasoconstrictor known, even more potent than endothelin-1. It was first isolated from the fish spinal cord and has been recognized as a hormone in the neurosecretory system of teleost fish for over 30 years. After the identification of U-II in humans and the orphan human G-protein-coupled receptor 14 as the urotensin II receptor, UT, many studies have shown that U-II may play an important role in cardiovascular regulation. Human urotensin II (hU-II) is an 11 amino acid cyclic peptide, generated by proteolytic cleavage from a precursor prohormone. It is expressed in the central nervous system as well as other tissues, such as kidney, spleen, small intestine, thymus, prostate, pituitary, and adrenal gland and circulates in human plasma. The plasma U-II level is elevated in renal failure, congestive heart failure, diabetes mellitus, systemic hypertension and portal hypertension caused by liver cirrhosis. The effect of U-II on the vascular system is variable, depending on species, vascular bed and calibre of the vessel. The net effect on vascular tone is a balance between endothelium-independent vasoconstriction and endothelium-dependent vasodilatation. U-II is also a neuropeptide and may play a role in tumour development. The development of UT receptor antagonists may provide a useful research tool as well as a novel treatment for cardiorenal diseases.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Bern HA, Pearson D, Larson BA, Nishioka RS. Neurohormones from fish tails: The caudal neurosecretory system. I. “Urophysiology” and the caudal necrosecretory system in fishes. Recent Prog Horm Res 1985;41:533–552.

    CAS  PubMed  Google Scholar 

  2. Ames RS, Sarau HM, Cambers JK, et al. Human urotensin II is a potent vasoconstrictor and agonist for the orphan receptor GPR14. Nature 1999;401:282–286.

    CAS  PubMed  Google Scholar 

  3. Coulouarn Y, Lihrmann I, Jegou S, et al. Cloning of the cDNA encoding the urotensin II precursor in frog and human reveals intense expression of the urotensin II gene in motoneurons of the spinal cord. Proc Natl Acad Sci USA 1998;95:15803–15808.

    CAS  PubMed  Google Scholar 

  4. Coulouarn Y, Jegou S, Tostivint H, Vaudry H, Lihrmann I. Cloning, sequence analysis and tissue distribution of the mouse and rat urotensin II precursors. FEBS Lett 1999;457:28–32.

    CAS  PubMed  Google Scholar 

  5. 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.

    CAS  PubMed  Google Scholar 

  6. Totsune K, Takahashi K, Arihara Z, et al. Role of urotensin II in patients on dialysis. Lancet 2001;358:810–811.

    CAS  PubMed  Google Scholar 

  7. Totsune K, Takahashi K, Arihara Z, Sone M, Ito S, Murakami O. Increased plasma urotensin II levels in patients with diabetes mellitus. Clin Sci 2003;104:1–5.

    CAS  PubMed  Google Scholar 

  8. Sugo T, Murakami Y, Shimomura Y, et al. Identification of urotensin II-related peptide as the urotensin II-immunoreactive molecule in the rat brain. Biochem Biophys Res Commun 2003;310:860–868.

    CAS  PubMed  Google Scholar 

  9. 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.

    CAS  PubMed  Google Scholar 

  10. Liu Q, Pong SS, Zeng Z, et al. Identification of urotensin II as the endogenous ligand for the orphan G-protein-coupled receptor GPR14. Biochem Biophys Res Commun 1999;266:174–178.

    CAS  PubMed  Google Scholar 

  11. 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.

    CAS  PubMed  Google Scholar 

  12. 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.

    CAS  PubMed  Google Scholar 

  13. Camarda V, Rizzi A, Calo G, et al. Effects of human urotensin II in isolated vessels of various species; comparison with other vasoactive agents. Naunyn Schmiedebergs Arch Pharmacol 2002;365:141–149.

    CAS  PubMed  Google Scholar 

  14. Saetrum Opgaard O, Nothacker H, Ehlert FJ, Krause DN. Human urotensin II mediates vasoconstriction via an increase in inositol phosphates. Eur J Pharmacol. 2000;406:265–271.

    CAS  PubMed  Google Scholar 

  15. 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.

    CAS  PubMed  Google Scholar 

  16. Russell FD. Emerging roles of urotensin-II in cardiovascular disease. Pharmacol Ther 2004;103:223–243.

    CAS  PubMed  Google Scholar 

  17. Yoshimoto T, Matsushita M, Hirata Y. Role of urotensin II in peripheral tissue as an autocrine/paracrine growth factor. Peptides 2004;25:1775–1781.

    CAS  PubMed  Google Scholar 

  18. Sauzeau V, Le Mellionnec E, 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.

    CAS  PubMed  Google Scholar 

  19. 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.

    CAS  PubMed  Google Scholar 

  20. Russell FD, Molenaar P. Investigation of signaling pathways that mediate the inotropic effect of urotensin-II in human heart. Cardiovasc Res. 2004;63:673–681.

    CAS  PubMed  Google Scholar 

  21. 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.

    CAS  PubMed  Google Scholar 

  22. 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.

    CAS  PubMed  Google Scholar 

  23. 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:H1576–H1581.

    CAS  PubMed  Google Scholar 

  24. 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.

    CAS  PubMed  Google Scholar 

  25. Nakayama K. Furin: A mammalian subtilisin/Kex2p-like endoprotease involved in processing of a wide variety of precursor proteins. Biochem J 1997;327:625–635.

    CAS  PubMed  Google Scholar 

  26. Mori M., Fujino M. Urotensin II-related peptide, the endogenous ligand for the urotensin II receptor in the rat brain. Peptides 2004;25:1815–1818.

    CAS  PubMed  Google Scholar 

  27. Aiyar N, Guida B, Ao Z, et al. Differential levels of “urotensin-II-like” activity determined by radio-receptor and radioimmuno-assays. Peptides 2004;25:1339–1347.

    CAS  PubMed  Google Scholar 

  28. Chatenet D, Dubessy C, Leprince J, et al. Structure-activity relationships and structural conformation of a novel urotensin II-related peptide. Peptides 2004;25:1819–1830.

    CAS  PubMed  Google Scholar 

  29. Chartrel N, Leprince J, Dujardin C, et al. Biochemical characterization and immunohistochemical localization of urotensin II in the human brainstem and spinal cord. J Neurochem 2004;91:110–118.

    CAS  PubMed  Google Scholar 

  30. Takahashi K, Totsune K, Murakami O, Shibahara S. Expression of urotensin II and urotensin II receptor mRNAs in various human tumor cell lines and secretion of urotensin II-like immunoreactivity by SW-13 adrenocortical carcinoma cells. Peptides 2001;22:1175–1179.

    CAS  PubMed  Google Scholar 

  31. Flohr S, Kurz M, Kostenis E, Brkovich A, Fournier A, Klabunde T. Identification of nonpeptidic urotensin II receptor antagonists by virtual screening based on a pharmacophore model derived from structure-activity relationships and nuclear magnetic resonance studies on urotensin II. J Med Chem 2002;45:1799–1805.

    CAS  PubMed  Google Scholar 

  32. Kinney WA, Almond Jr HR, Qi J, et al. Structure-function analysis of urotensin II and its use in the construction of a ligand-receptor working model. Angew Chem Int Ed Engl 2002;41:2940–2944.

    CAS  PubMed  Google Scholar 

  33. Brkovic A, Hattenberger A, Kostenis E, et al. Functional and binding characterizations of urotensin II-related peptides in human and rat urotensin II-receptor assay. J Pharmacol Exp Ther 2003;306:1200–1209.

    CAS  PubMed  Google Scholar 

  34. Boucard AA, Sauve SS, Guillemette G, Escher E, Leduc R. Photolabelling the rat urotensin II/GPR14 receptor identifies a ligand-binding site in the fourth transmembrane domain. Biochem J 2003;370:829–838.

    CAS  PubMed  Google Scholar 

  35. Grieco P, Carotenuto A, Patacchini R, Maggi CA, Novellino E, Rovero P. Design, synthesis, conformational analysis, and biological studies of urotensin-II lactam analogues. Bioorg Med Chem 2002;10:3731–3739.

    CAS  PubMed  Google Scholar 

  36. Grieco P, Carotenuto A, Campiglia P, et al. A new, potent urotensin II receptor peptide agonist containing a Pen residue at the disulfide bridge. J Med Chem 2002;45:4391–4394.

    CAS  PubMed  Google Scholar 

  37. Camarda V, Guerrini R, Kostenis E, et al. A new ligand for the urotensin II receptor. Br J Pharmacol 2002;137:311–314.

    CAS  PubMed  Google Scholar 

  38. 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.

    CAS  PubMed  Google Scholar 

  39. Camarda V, Song W, Marzola E, et al. Urantide mimics urotensin-II induced calcium release in cells expressing recombinant UT receptors. Eur J Pharmacol 2004;498:83–86.

    CAS  PubMed  Google Scholar 

  40. Coy DH, Rossowski WJ, Cheng BL, Hocart SJ, Taylor JE. Novel urotensin-II (UII) antagonists point to multiple receptor involvement in UII bioactivity. Reg Pep 2000; 94:48.

    Google Scholar 

  41. Behm DJ, Herold CL, Ohlstein EH, Knight SD, Dhanak D, Douglas SA. 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 2002;137:449–458.

    CAS  PubMed  Google Scholar 

  42. Herold CL, Behm DJ, Aiyar NV, et al. The somatostatin derivative, Cpa-c-[D-Cys-Pal-D-Trp-Lys-Val-Cys]-Cpa-amide, is an agonist at the human UT receptor but not the rat UT receptor in transfected HEK293 cells. Pharmacologist 2001;43:189.

    Google Scholar 

  43. Behm DJ, Herold CL, Camarda V, Aiyar NV, Douglas SA. Differential agonistic and antagonistic effects of the urotensin-II ligand SB-710411 at rodent and primate UT receptors. Eur J Pharmacol 2004;492:113–116.

    CAS  PubMed  Google Scholar 

  44. Herold CL, Behm DJ, Buckley PT, et al. The neuromedin B receptor antagonist, BIM-23127, is a potent antagonist at human and rat urotensin-II receptors. Br J Pharmacol 2003;139:203–207.

    CAS  PubMed  Google Scholar 

  45. Croston GE, Olsson R, Currier EA, et al. Discovery of the first nonpeptide agonist of the GPR14/urotensin-II receptor: 3-(4-chlorophenyl)-3-(2-(dimethylamino)ethyl)isochroman-1-one (AC-7954). J Med Chem 2002;45:4950–4953.

    CAS  PubMed  Google Scholar 

  46. 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.

    CAS  PubMed  Google Scholar 

  47. Gibson A. Complex effects of Gillichthys urotensin II on rat aortic strips. Br J Pharmacol 1987;91:205–212.

    CAS  PubMed  Google Scholar 

  48. Itoh H, Itoh Y, Rivier J, Lederis K. Contraction of major artery segments of rat by fish neuropeptide urotensin II. Am J Physiol 1987;252:R361–R366.

    CAS  PubMed  Google Scholar 

  49. Behm DJ, Harrison SM, Ao Z, 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.

    CAS  PubMed  Google Scholar 

  50. MacLean MR, Alexander D, Stirrat A, 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.

    CAS  PubMed  Google Scholar 

  51. Bennett RT, Jones RD, Morice AH, Smith CF, 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.

    CAS  PubMed  Google Scholar 

  52. Douglas SA, Ashton DJ, Sauermelch CF, et al. Human urotensin-II is a potent vasoactive peptide: Pharmacological characterization in the rat, mouse, dog and primate. J Cardiovasc Pharmacol 2000;36(Suppl 1):S163–S166.

    CAS  PubMed  Google Scholar 

  53. 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.

    CAS  PubMed  Google Scholar 

  54. 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.

    CAS  PubMed  Google Scholar 

  55. 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.

    CAS  PubMed  Google Scholar 

  56. Itoh H, McMaster D, Lederis K. Functional receptors for fish neuropeptide urotensin II in major rat arteries. Eur J Pharmacol 1988;149:61–66.

    CAS  PubMed  Google Scholar 

  57. 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.

    CAS  PubMed  Google Scholar 

  58. Katano Y, Ishihata A, Aita T, Ogaki T, Horie T. Vasodilator effect of urotensin II, one of the most potent vasoconstricting factors, on rat coronary arteries. Eur J Pharmacol 2000;402:R5–R7.

    CAS  PubMed  Google Scholar 

  59. Zhang AY, Chen YF, Zhang DX, et al. Urotensin II is a nitric oxide-dependent vasodilator and natriuretic peptide in the rat kidney. Am J Physiol Renal Physiol 2003;285:F792–F798.

    CAS  PubMed  Google Scholar 

  60. Kelly RA, Balligand JL, Smith TW. Nitric oxide and cardiac function. Circ Res 1996;79:363–380.

    CAS  PubMed  Google Scholar 

  61. Li L, Yuan WJ, Su DF. Effects of rat urotensin II on coronary flow and myocardial eNOS protein expression in isolated rat heart. Acta Pharmacol Sin 2004;25:1444–1449.

    CAS  PubMed  Google Scholar 

  62. Russell FD, Molenaar P, O’Brien DM. Cardiostimulant effects of urotensin-II in human heart in vitro. Br J Pharmacol 2001;132:5–9.

    CAS  PubMed  Google Scholar 

  63. 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 Physiol Pharmacol 2004;82:16–21.

    CAS  PubMed  Google Scholar 

  64. Gardiner SM, March JE, Kemp PA, Bennett T. Bolus injection of human UII in conscious rats evokes a biphasic haemodynamic response. Br J Pharmacol 2004;143:422–430.

    CAS  PubMed  Google Scholar 

  65. Gardiner SM, March JE, Kemp PA, Davenport AP, Bennett T. Depressor and regionally-selective vasodilator effects of human and rat urotensin II in conscious rats. Br J Pharmacol 2001;132:1625–1629.

    CAS  PubMed  Google Scholar 

  66. Zhu YZ, Wang ZJ, Zhu YC, et al. Urotensin II causes fatal circulatory collapse in anesthesized monkeys in vivo: A “vasoconstrictor” with a unique hemodynamic profile. Am J Physiol Heart Circ Physiol 2004;286:H830–H836.

    CAS  PubMed  Google Scholar 

  67. Hassan GS, Chouiali F, Saito T, et al. Effect of human urotensin-II infusion on hemodynamics and cardiac function. Can J Physiol Pharmacol 2003;81:125–128.

    CAS  PubMed  Google Scholar 

  68. Behm DJ, Doe CP, Johns DG, et al. Urotensin-II: A novel systemic hypertensive factor in the cat. Naunyn Schmiedebergs Arch Pharmacol 2004;369:274–280.

    CAS  PubMed  Google Scholar 

  69. Bohm F, Pernow J. Urotensin II evokes potent vasoconstriction in humans in vivo. Br J Pharmacol 2002;135:25–27.

    CAS  PubMed  Google Scholar 

  70. 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.

    CAS  PubMed  Google Scholar 

  71. 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.

    CAS  PubMed  Google Scholar 

  72. Lim M, Honisett S, Sparkes CD, Komesaroff P, Kompa A, Krum H. Differential effect of urotensin II on vascular tone in normal subjects and patients with chronic heart failure. Circulation 2004;109:1212–1214.

    CAS  PubMed  Google Scholar 

  73. Shenouda A, Douglas SA, Ohlstein EH, Giaid A. Localization of urotensin-II immunoreactivity in normal human kidneys and renal carcinoma. J Histochem Cytochem 2002;50:885–889.

    CAS  PubMed  Google Scholar 

  74. Pelletier G, Lihrmann I, Vaudry H. Role of androgens in the regulation of urotensin II precursor mRNA expression in the rat brainstem and spinal cord. Neuroscience 2002;115:525–532.

    CAS  PubMed  Google Scholar 

  75. Nordeen EJ, Nordeen KW, Sengelaub DR, Arnold AP. Androgens prevent normally occurring cell death in a sexually dimorphic spinal nucleus. Science 1985;229:671–673.

    CAS  PubMed  Google Scholar 

  76. Kurz EM, Sengelaub DR, Arnold AP. Androgens regulate the dendritic length of mammalian motoneurons in adulthood. Science 1986;232:395–398.

    CAS  PubMed  Google Scholar 

  77. Yu WH. Administration of testosterone attenuates neuronal loss following axotomy in the brain-stem motor nuclei of female rats. J Neurosci 1989;9:3908–3914.

    CAS  PubMed  Google Scholar 

  78. Gibson SJ, Polak JM, Bloom SR, et al. Calcitonin gene-related peptide immunoreactivity in the spinal cord of man and of eight other species. J Neurosci 1984;4:3101–3111.

    CAS  PubMed  Google Scholar 

  79. Brailoiu E, Brailoiu GC, Miyamoto MD, Dun NJ. The vasoactive peptide urotensin II stimulates spontaneous release from frog motor nerve terminals. Br J Pharmacol 2003;138:1580–1588.

    CAS  PubMed  Google Scholar 

  80. Gartlon JE, Ashmeade T, Duxon M, Hagan JJ, Jones DN. Urotensin-II, a neuropeptide ligand for GPR14, induces c-fos in the rat brain. Eur J Pharmacol 2004;493:95–98.

    CAS  PubMed  Google Scholar 

  81. Gartlon J, Parker F, Harrison DC, et al. Central effects of urotensin-II following ICV administration in rats. Psychopharmacology (Berl) 2001; 155:426–433.

    CAS  Google Scholar 

  82. 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.

    CAS  PubMed  Google Scholar 

  83. Lu Y, Zou CJ, Huang DW, Tang CS. Cardiovascular effects of urotensin II in different brain areas. Peptides 2002;23:1631–1635.

    CAS  PubMed  Google Scholar 

  84. Watson AM, 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.

    CAS  PubMed  Google Scholar 

  85. Filipeanu CM, Brailoiu E, Le Dun S, Dun NJ. Urotensin-II regulates intracellular calcium in dissociated rat spinal cord neurons. J Neurochem 2002;83:879–884.

    CAS  PubMed  Google Scholar 

  86. Ng LL, Loke I, O’Brien RJ, Squire IB, Davies JE. Plasma urotensin in human systolic heart failure. Circulation 2002;106:2877–2880.

    CAS  PubMed  Google Scholar 

  87. Richards AM, Nicholls MG, Lainchbury JG, Fisher S, Yandle TG. Plasma urotensin II in heart failure. Lancet 2002;360:545–546.

    CAS  PubMed  Google Scholar 

  88. 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.

    PubMed  Google Scholar 

  89. Douglas SA, Tayara L, Ohlstein EH, Halawa N, Giaid A. Congestive heart failure and expression of myocardial urotensin II. Lancet 2002;359:1990–1997.

    CAS  PubMed  Google Scholar 

  90. Cheung BM, Leung R, Man YB, Wong LY. Plasma concentration of urotensin II is raised in hypertension. J Hypertens 2004;22:1341–1344.

    CAS  PubMed  Google Scholar 

  91. 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 Hepato. 2002;37:767– 772.

    CAS  Google Scholar 

  92. 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.

    CAS  PubMed  Google Scholar 

  93. Langham RG, Kelly DJ, Gow RM, et al. Increased expression of urotensin II and urotensin II receptor in human diabetic nephropathy. Am J Kidney Dis 2004;44:826–831.

    CAS  PubMed  Google Scholar 

  94. Silvestre RA, Rodriguez-Gallardo J, Egido EM, Marco J. Inhibition of insulin release by urotensin II–a study on the perfused rat pancreas. Horm Metab Res 2001;33:379– 381.

    CAS  PubMed  Google Scholar 

  95. 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.

    CAS  PubMed  Google Scholar 

  96. Zhu F, Ji L, Luo B. The role of urotensin II gene in the genetic susceptibility to type 2 diabetes in Chinese population. Zhonghua Yi Xue Za Zhi 2002;82:1473–1475.

    CAS  PubMed  Google Scholar 

  97. Wenyi Z, Suzuki S, Hirai M, et al. Role of urotensin II gene in genetic susceptibility to type 2 diabetes mellitus in Japanese subjects. Diabetologia 2003;46:972–976.

    CAS  PubMed  Google Scholar 

  98. 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 Japanese. Peptides 2004;25:1803–1808.

    CAS  PubMed  Google Scholar 

  99. 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.

    CAS  PubMed  Google Scholar 

  100. Budhiraja R, Tuder RM, Hassoun PM. Endothelial dysfunction in pulmonary hypertension. Circulation 2004;109:159–165.

    PubMed  Google Scholar 

  101. Qi J, Du J, Tang X, Li J, Wei B, Tang C. The upregulation of endothelial nitric oxide synthase and urotensin-II is associated with pulmonary hypertension and vascular diseases in rats produced by aortocaval shunting. Heart Vessels 2004;19:81–88.

    PubMed  Google Scholar 

  102. Zhang Y, Li J, Cao J, et al. Effect of chronic hypoxia on contents of urotensin II and its functional receptors in rat myocardium. Heart Vessels 2002;16:64–68.

    Article  PubMed  Google Scholar 

  103. 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.

    CAS  PubMed  Google Scholar 

  104. 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.

    Article  CAS  PubMed  Google Scholar 

  105. 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.

    Article  CAS  PubMed  Google Scholar 

  106. Zou Y, Nagai R, Yamazaki T. Urotensin II induces hypertrophic responses in cultured cardiomyocytes from neonatal rats. FEBS Lett 2001;508:57–60.

    Article  CAS  PubMed  Google Scholar 

  107. Zuo HH, Jie-Min H, Guo HS, et al. Urotensin II induces hypertrophy of in vitro cultured neonatal rat cardiac myocytes. Di Yi Jun Yi Da Xue Xue Bao 2004;24:642–645.

    CAS  PubMed  Google Scholar 

  108. Onan D, Pipolo L, Yang E, Hannan RD, Thomas WG. Urotensin-II Promotes Hypertrophy of Cardiac Myocytes via Mitogen-Activated Protein Kinases. Mol Endocrinol 2004;18:2344–2354.

    Article  CAS  PubMed  Google Scholar 

  109. 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.

    Article  CAS  PubMed  Google Scholar 

  110. 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.

    Article  CAS  PubMed  Google Scholar 

  111. He YH, Hong JM, Guo HS, et al. Effects of urotensin II on cultured cardiac fibroblast proliferation and collagen type I mRNA expression. Di Yi Jun Yi Da Xue Xue Bao 2004;24:505–508.

    CAS  PubMed  Google Scholar 

  112. 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.

    Article  PubMed  Google Scholar 

  113. Takahashi K, Totsune K, Murakami O, et al. Expression of urotensin II and its receptor in adrenal tumors and stimulation of proliferation of cultured tumor cells by urotensin II. Peptides 2003;24:301–306.

    Article  CAS  PubMed  Google Scholar 

  114. Matsushita M, Shichiri M, Fukai N, et al. Urotensin II is an autocrine/paracrine growth factor for the porcine renal epithelial cell line, LLCPK1. Endocrinology 2003;144:1825–1831.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Medicine and the Research Centre of Heart, Brain, Hormone and Healthy Aging, University of Hong Kong, Hong Kong

    Kwok Leung Ong, Karen S. L. Lam & Bernard M. Y. Cheung M.A., MB BChir, Ph.D., FRCP, FRCPE, FCP

  2. Department of Medicine, Queen Mary Hospital, University of Hong Kong, Pokfulam, Hong Kong

    Bernard M. Y. Cheung M.A., MB BChir, Ph.D., FRCP, FRCPE, FCP

Authors
  1. Kwok Leung Ong
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Karen S. L. Lam
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Bernard M. Y. Cheung M.A., MB BChir, Ph.D., FRCP, FRCPE, FCP
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Bernard M. Y. Cheung M.A., MB BChir, Ph.D., FRCP, FRCPE, FCP.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ong, K.L., Lam, K.S.L. & Cheung, B.M.Y. Urotensin II: Its Function in Health and Its Role in Disease. Cardiovasc Drugs Ther 19, 65–75 (2005). https://doi.org/10.1007/s10557-005-6899-x

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10557-005-6899-x

Key Words

Search

Navigation