Journal of Anesthesia

, 21:378 | Cite as

Role of urotensin II and its receptor in health and disease

  • John McDonald
  • Madura Batuwangala
  • David G. Lambert
Review articles


Urotensin II (U-II) is currently the most potent vasoconstrictor identified. This action is brought about via activation of a Gq/11-protein coupled receptor (UT receptor). U-II activation of the UT receptor increases inositol phosphate turnover and intracellular Ca2+. In addition to producing vasoconstriction, dilation and ionotropic effects have also been described. There is considerable variation in the responsiveness of particular vascular beds from the same and different species, including humans. Receptors for U-II are located peripherally on vascular smooth muscle (contractile responses) and endothelial cells (dilatory responses via nitric oxide). In humans, plasma U-II is elevated in heart failure, renal failure, liver disease, and diabetes. Iontophoresis of U-II in healthy volunteers produces vasodilation (of the forearm) while in patients with heart failure or hypertension a constriction is observed. To date there is only one clinical study using a UT receptor antagonist (palosuran) in diabetic patients with macroalbuminuria. This antagonist reduced albumin excretion, probably by increasing renal blood flow. Studies in other disease conditions are eagerly awaited. In summary, the U-II / UT receptor system has clinical potential, and for the anesthesiologist, this novel peptide-receptor system may be of use in the intensive care unit.

Key words

Urotensin II Pharmacology Heart disease Diabetes Renal failure 


  1. 1.
    Onan, D, Hannan, RD, Thomas, WG 2004Urotensin II: the old kid in townTrends Endocrinol Metab15175182PubMedCrossRefGoogle Scholar
  2. 2.
    Ames, RS, Sarau, HM, Chambers, JK, Willette, RN, Aiyar, NV, Romanic, AM, Louden, CS, Foley, JJ, Sauermelch, CF, Coatney, RW, Ao, Z, Disa, J, Holmes, SD, Stadel, JM, Martin, JD, Liu, WS, Glover, GI, Wilson, S, McNulty, DE, Ellis, CE, Elshourbagy, NA, Shabon, U, Trill, JJ, Hay, DW, Douglas, SA 1999Human urotensin-II is a potent vasoconstrictor and agonist for the orphan receptor GPR14Nature401282286PubMedCrossRefGoogle Scholar
  3. 3.
    Stirrat, A, Gallagher, M, Douglas, SA, Ohlstein, EH, Berry, C, Kirk, A, Richardson, M, MacLean, MR 2001Potent vasodilator responses to human urotensin-II in human pulmonary and abdominal resistance arteriesAm J Physiol Heart Circ Physiol280H925928PubMedGoogle Scholar
  4. 4.
    Russell, FD, Molenaar, P, O'Brien, DM 2001Cardiostimulant effects of urotensin-II in human heart in vitroBr J Pharmacol13259PubMedCrossRefGoogle Scholar
  5. 5.
    Matsushita, M, Shichiri, M, Imai, T, Iwashina, M, Tanaka, H, Takasu, N, Hirata, Y 2001Co-expression of urotensin II and its receptor (GPR14) in human cardiovascular and renal tissuesJ Hypertens1921852190PubMedCrossRefGoogle Scholar
  6. 6.
    Jegou, S, Cartier, D, Dubessy, C, Gonzalez, BJ, Chatenet, D, Tostivint, H, Scalbert, E, LePrince, J, Vaudry, H, Lihrmann, I 2006Localization of the urotensin II receptor in the rat central nervous systemJ Comp Neurol4952136PubMedCrossRefGoogle Scholar
  7. 7.
    Davenport, AP, Maguire, JJ 2000Urotensin II: fish neuropeptide catches orphan receptorTrends Pharmacol Sci218082PubMedCrossRefGoogle Scholar
  8. 8.
    Ong, KL, Lam, KS, Cheung, BM 2005Urotensin II: its function in health and its role in diseaseCardiovasc Drugs Ther196575PubMedCrossRefGoogle Scholar
  9. 9.
    Zhu, YC, Zhu, YZ, Moore, PK 2006The role of urotensin II in cardiovascular and renal physiology and diseasesBr J Pharmacol148884901PubMedCrossRefGoogle Scholar
  10. 10.
    Douglas, SA, Dhanak, D, Johns, DG 2004From “gills to pills”: urotensin-II as a regulator of mammalian cardiorenal functionTrends Pharmacol Sci257685PubMedCrossRefGoogle Scholar
  11. 11.
    Douglas, SA 2003Human urotensin-II as a novel cardiovascular target: “heart” of the matter or simply a fishy “tailCurr Opin Pharmacol3159167PubMedCrossRefGoogle Scholar
  12. 12.
    Watson, AM, May, CN 2004Urotensin II, a novel peptide in central and peripheral cardiovascular controlPeptides2517591766PubMedCrossRefGoogle Scholar
  13. 13.
    Douglas, SA, Ohlstein, EH 2000Human urotensin-II, the most potent mammalian vasoconstrictor identified to date, as a therapeutic target for the management of cardiovascular diseaseTrends Cardiovasc Med10229237PubMedCrossRefGoogle Scholar
  14. 14.
    Douglas, SA, Ohlstein, EH 2000

    Urotensin receptors

    Girdlestone, D eds. The IUPHAR compendium of receptor characterisation and classificationIUPHAR MediaLondon365372
    Google Scholar
  15. 15.
    Camarda, V, Guerrini, R, Kostenis, E, Rizzi, A, Calo, G, Hattenberger, A, Zucchini, M, Salvadori, S, Regoli, D 2002A new ligand for the urotensin II receptorBr J Pharmacol137311314PubMedCrossRefGoogle Scholar
  16. 16.
    Douglas, SA, Naselsky, D, Ao, Z, Disa, J, Herold, CL, Lynch, F, Aiyar, NV 2004Identification and pharmacological characterization of native, functional human urotensin-II receptors in rhabdomyosarcoma cell linesBr J Pharmacol142921932PubMedCrossRefGoogle Scholar
  17. 17.
    Song, W, McDonald, J, Camarda, V, Calo, G, Guerrini, R, Marzola, E, Thompson, JP, Rowbotham, DJ, Lambert, DG 2006Cell and tissue responses of a range of urotensin II analogs at cloned and native urotensin II receptors. Evidence for coupling promiscuityNaunyn Schmiedebergs Arch Pharmacol373148157PubMedCrossRefGoogle Scholar
  18. 18.
    Filipeanu, CM, Brailoiu, E, Le Dun, S, Dun, NJ 2002Urotensin-II regulates intracellular calcium in dissociated rat spinal cord neuronsJ Neurochem83879884PubMedCrossRefGoogle Scholar
  19. 19.
    Mori, M, Sugo, T, Abe, M, Shimomura, Y, Kurihara, M, Kitada, C, Kikuchi, K, Shintani, Y, Kurokawa, T, Onda, H, Nishimura, O, Fujino, M 1999Urotensin II is the endogenous ligand of a G-protein-coupled orphan receptor, SENR (GPR14)Biochem Biophys Res Commun265123129PubMedCrossRefGoogle Scholar
  20. 20.
    Coulouarn, Y, Lihrmann, I, Jegou, S, Anouar, Y, Tostivint, H, Beauvillain, JC, Conlon, JM, Bern, HA, Vaudry, H 1998Cloning 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 cordProc Natl Acad Sci USA951580315808PubMedCrossRefGoogle Scholar
  21. 21.
    Bern, HA, Pearson, D, Larson, BA, Nishioka, RS 1985Neurohormones from fish tails: the caudal neurosecretory system. I. “Urophysiology” and the caudal neurosecretory system of fishesRecent Prog Horm Res41533552PubMedGoogle Scholar
  22. 22.
    Kinney, WA, Almond, HR,Jr, Qi, J, Smith, CE, Santulli, RJ, de Garavilla, L, Andrade-Gordon, P, Cho, DS, Everson, AM, Feinstein, MA, Leung, PA, Maryanoff, BE 2002Structure-function analysis of urotensin II and its use in the construction of a ligand-receptor working modelAngew Chem Int Ed Engl4129402944PubMedCrossRefGoogle Scholar
  23. 23.
    Mori, M, Fujino, M 2004Urotensin II-related peptide, the endogenous ligand for the urotensin II receptor in the rat brainPeptides2518151818PubMedCrossRefGoogle Scholar
  24. 24.
    Sugo, T, Murakami, Y, Shimomura, Y, Harada, M, Abe, M, Ishibashi, Y, Kitada, C, Miyajima, N, Suzuki, N, Mori, M, Fujino, M 2003Identification of urotensin II-related peptide as the urotensin II-immunoreactive molecule in the rat brainBiochem Biophys Res Commun310860868PubMedCrossRefGoogle Scholar
  25. 25.
    Flohr, S, Kurz, M, Kostenis, E, Brkovich, A, Fournier, A, Klabunde, T 2002Identification 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 IIJ Med Chem4517991805PubMedCrossRefGoogle Scholar
  26. 26.
    Camarda, V, Spagnol, M, Song, W, Vergura, R, Roth, AL, Thompson, JP, Rowbotham, DJ, Guerrini, R, Marzola, E, Salvadori, S, Cavanni, P, Regoli, D, Douglas, SA, Lambert, DG, Calo, G 2006In vitro and in vivo pharmacological characterization of the novel UT receptor ligand [Pen(5),DTrp(7),Dab(8)]urotensin II(4-11) (UFP-803)Br J Pharmacol14792100PubMedCrossRefGoogle Scholar
  27. 27.
    Patacchini, R, Santicioli, P, Giuliani, S, Grieco, P, Novellino, E, Rovero, P, Maggi, CA 2003Urantide: an ultrapotent urotensin II antagonist peptide in the rat aortaBr J Pharmacol14011551158PubMedCrossRefGoogle Scholar
  28. 28.
    Camarda, V, Song, W, Marzola, E, Spagnol, M, Guerrini, R, Salvadori, S, Regoli, D, Thompson, JP, Rowbotham, DJ, Behm, DJ, Douglas, SA, Calo, G, Lambert, DG 2004Urantide mimics urotensin-II induced calcium release in cells expressing recombinant UT receptorsEur J Pharmacol4988386PubMedCrossRefGoogle Scholar
  29. 29.
    Clozel, M, Binkert, C, Birker-Robaczewska, M, Boukhadra, C, Ding, SS, Fischli, W, Hess, P, Mathys, B, Morrison, K, Muller, C, Muller, C, Nayler, O, Qiu, C, Rey, M, Scherz, MW, Velker, J, Weller, T, Xi, JF, Ziltener, P 2004Pharmacology 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 SystemJ Pharmacol Exp Ther311204212PubMedCrossRefGoogle Scholar
  30. 30.
    Croston, GE, Olsson, R, Currier, EA, Burstein, ES, Weiner, D, Nash, N, Severance, D, Allenmark, SG, Thunberg, L, Ma, JN, Mohell, N, O'Dowd, B, Brann, MR, Hacksell, U 2002Discovery 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 Chem4549504953PubMedCrossRefGoogle Scholar
  31. 31.
    Douglas, SA, Behm, DJ, Aiyar, NV, Naselsky, D, Disa, J, Brooks, DP, Ohlstein, EH, Gleason, JG, Sarau, HM, Foley, JJ, Buckley, PT, Schmidt, DB, Wixted, WE, Widdowson, K, Riley, G, Jin, J, Gallagher, TF, Schmidt, SJ, Ridgers, L, Christmann, LT, Keenan, RM, Knight, SD, Dhanak, D 2005Nonpeptidic urotensin-II receptor antagonists I: in vitro pharmacological characterization of SB-706375. BrJ Pharmacol145620635Google Scholar
  32. 32.
    Carotenuto, A, Grieco, P, Rovero, P, Novellino, E 2006Urotensin-II receptor antagonistsCurr Med Chem13267275PubMedCrossRefGoogle Scholar
  33. 33.
    Gibson, A, Conyers, S, Bern, HA 1988The influence of urotensin II on calcium flux in rat aortaJ Pharm Pharmacol40893895PubMedGoogle Scholar
  34. 34.
    Camarda, V, Rizzi, A, Calo, G, Gendron, G, Perron, SI, Kostenis, E, Zamboni, P, Mascoli, F, Regoli, D 2002Effects of human urotensin II in isolated vessels of various species; comparison with other vasoactive agentsNaunyn Schmiedebergs Arch Pharmacol365141149PubMedCrossRefGoogle Scholar
  35. 35.
    Saetrum Opgaard, O, Nothacker, H, Ehlert, FJ, Krause, DN 2000Human urotensin II mediates vasoconstriction via an increase in inositol phosphatesEur J Pharmacol406265271PubMedCrossRefGoogle Scholar
  36. 36.
    Maguire, JJ, Davenport, AP 2002Is urotensin-II the new endothelin?Br J Pharmacol137579588PubMedCrossRefGoogle Scholar
  37. 37.
    Batuwangala, M, McDonald, J, Calo, G, Ng, LL, Lambert, DG 2006Characterization of native urotensin II receptors expressed in SJCRH30 rhabdomyosarcoma cellsBr J Anaesth97440Google Scholar
  38. 38.
    Onan, D, Pipolo, L, Yang, E, Hannan, RD, Thomas, WG 2004Urotensin II promotes hypertrophy of cardiac myocytes via mitogen-activated protein kinasesMol Endocrinol1823442354PubMedCrossRefGoogle Scholar
  39. 39.
    Sugden, PH, Clerk, A 1998Cellular mechanisms of cardiac hypertrophyJ Mol Med76725746PubMedCrossRefGoogle Scholar
  40. 40.
    Clerk, A, Sugden, PH 1999Activation of protein kinase cascades in the heart by hypertrophic G protein-coupled receptor agonistsAm J Cardiol8364H69HPubMedCrossRefGoogle Scholar
  41. 41.
    Ziltener, P, Mueller, C, Haenig, B, Scherz, MW, Nayler, O 2002Urotensin II mediates ERK1/2 phosphorylation and proliferation in GPR14-transfected cell linesJ Recept Signal Transduct Res22155168PubMedCrossRefGoogle Scholar
  42. 42.
    Luscher, TF 1991Endothelium-derived nitric oxide: the endogenous nitrovasodilator in the human cardiovascular systemEur Heart J12211PubMedGoogle Scholar
  43. 43.
    Moncada S, Higgs EA (2006) Nitric oxide and the vascular endothelium. Handb Exp Pharmacol 213–254Google Scholar
  44. 44.
    Camarda, V, Rizzi, A, Calo, G, Gendron, G, Perron, SI, Kostenis, E, Zamboni, P, Mascoli, F, Regoli, D 2002Effects of human urotensin II in isolated vessels of various species; comparison with other vasoactive agentsNaunyn Schmiedebergs Arch Pharmacol365141149PubMedCrossRefGoogle Scholar
  45. 45.
    Douglas, SA, Sulpizio, AC, Piercy, V, Sarau, HM, Ames, RS, Aiyar, NV, Ohlstein, EH, Willette, RN 2000Differential vasoconstrictor activity of human urotensin-II in vascular tissue isolated from the rat, mouse, dog, pig, marmoset and cynomolgus monkeyBr J Pharmacol13112621274PubMedCrossRefGoogle Scholar
  46. 46.
    Itoh, H, McMaster, D, Lederis, K 1988Functional receptors for fish neuropeptide urotensin II in major rat arteriesEur J Pharmacol1496166PubMedCrossRefGoogle Scholar
  47. 47.
    Ishihata, A, Sakai, M, Katano, Y 2006Vascular contractile effect of urotensin II in young and aged rats: influence of aging and contribution of endothelial nitric oxidePeptides278086PubMedCrossRefGoogle Scholar
  48. 48.
    Bottrill, FE, Douglas, SA, Hiley, CR, White, R 2000Human urotensin-II is an endothelium-dependent vasodilator in rat small arteriesBr J Pharmacol13018651870PubMedCrossRefGoogle Scholar
  49. 49.
    MacLean, MR, Alexander, D, Stirrat, A, Gallagher, M, Douglas, SA, Ohlstein, EH, Morecroft, I, Polland, K 2000Contractile responses to human urotensin-II in rat and human pulmonary arteries: effect of endothelial factors and chronic hypoxia in the ratBr J Pharmacol130201204PubMedCrossRefGoogle Scholar
  50. 50.
    Muramatsu, I, Fujiwara, M, Hidaka, H, Akutagawa, H 1979

    Pharmacological analysis of urotensin-induced contraction and relaxation in isolated rabbit aortas

    Yamamoto, K eds. The caudal neurosecretory system of fishes (16th Gunma Symposium in Endocrinology)Gunma UniversityMaebashi, Japan3947
    Google Scholar
  51. 51.
    Gardiner, SM, March, JE, Kemp, PA, Davenport, AP, Bennett, T 2001Depressor and regionally-selective vasodilator effects of human and rat urotensin II in conscious ratsBr J Pharmacol13216251629PubMedCrossRefGoogle Scholar
  52. 52.
    Gardiner, SM, March, JE, Kemp, PA, Maguire, JJ, Kuc, RE, Davenport, AP, Bennett, T 2006Regional heterogeneity in the haemodynamic responses to urotensin II infusion in relation to UT receptor localisationBr J Pharmacol147612621PubMedCrossRefGoogle Scholar
  53. 53.
    Gray, GA, Jones, MR, Sharif, I 2001Human urotensin II increases coronary perfusion pressure in the isolated rat heart: potentiation by nitric oxide synthase and cyclooxygenase inhibitionLife Sci69175180PubMedCrossRefGoogle Scholar
  54. 54.
    Behm, DJ, Harrison, SM, Ao, Z, Maniscalco, K, Pickering, SJ, Grau, EV, Woods, TN, Coatney, RW, Doe, CP, Willette, RN, Johns, DG, Douglas, SA 2003Deletion of the UT receptor gene results in the selective loss of urotensin-II contractile activity in aortae isolated from UT receptor knockout miceBr J Pharmacol139464472PubMedCrossRefGoogle Scholar
  55. 55.
    Wang, ZJ, Shi, LB, Xiong, ZW, Zhang, LF, Meng, L, Bu, DF, Tang, CS, Ding, WH 2006Alteration of vascular urotensin II receptor in mice with apolipoprotein E gene knockoutPeptides27858863PubMedCrossRefGoogle Scholar
  56. 56.
    Coulouarn, Y, Fernex, C, Jegou, S, Henderson, CE, Vaudry, H, Lihrmann, I 2001Specific expression of the urotensin II gene in sacral motoneurons of developing rat spinal cordMech Dev101187190PubMedCrossRefGoogle Scholar
  57. 57.
    Dun, SL, Brailoiu, GC, Yang, J, Chang, JK, Dun, NJ 2001Urotensin II-immunoreactivity in the brainstem and spinal cord of the ratNeurosci Lett305912PubMedCrossRefGoogle Scholar
  58. 58.
    Lin, Y, Tsuchihashi, T, Matsumura, K, Abe, I, Iida, M 2003Central cardiovascular action of urotensin II in conscious ratsJ Hypertens21159165PubMedCrossRefGoogle Scholar
  59. 59.
    Watson, AM, Lambert, GW, Smith, KJ, May, CN 2003Urotensin II acts centrally to increase epinephrine and ACTH release and cause potent inotropic and chronotropic actionsHypertension42373379PubMedCrossRefGoogle Scholar
  60. 60.
    Maguire, JJ, Kuc, RE, Davenport, AP 2000Orphan-receptor ligand human urotensin II: receptor localization in human tissues and comparison of vasoconstrictor responses with endothelin-1. BrJ Pharmacol131441446Google Scholar
  61. 61.
    Totsune, K, Takahashi, K, Arihara, Z, Sone, M, Ito, S, Murakami, O 2003Increased plasma urotensin II levels in patients with diabetes mellitusClin Sci (Lond)10415CrossRefGoogle Scholar
  62. 62.
    Heller, J, Schepke, M, Neef, M, Woitas, R, Rabe, C, Sauerbruch, T 2002Increased urotensin II plasma levels in patients with cirrhosis and portal hypertensionJ Hepatol37767772PubMedCrossRefGoogle Scholar
  63. 63.
    Aiyar, N, Guida, B, Ao, Z, Disa, J, Naselsky, D, Behm, DJ, Su, JL, Kull, FC, Douglas, SA,Jr 2004Differential levels of “urotensin-II-like” activity determined by radio-receptor and radioimmuno-assaysPeptides2513391347PubMedCrossRefGoogle Scholar
  64. 64.
    Douglas, SA, Tayara, L, Ohlstein, EH, Halawa, N, Giaid, A 2002Congestive heart failure and expression of myocardial urotensin IILancet35919901997PubMedCrossRefGoogle Scholar
  65. 65.
    Lim, M, Honisett, S, Sparkes, CD, Komesaroff, P, Kompa, A, Krum, H 2004Differential effect of urotensin II on vascular tone in normal subjects and patients with chronic heart failureCirculation10912121214PubMedCrossRefGoogle Scholar
  66. 66.
    Thompson, JP, Watt, P, Sanghavi, S, Strupish, JW, Lambert, DG 2003A comparison of cerebrospinal fluid and plasma urotensin II concentrations in normotensive and hypertensive patients undergoing urological surgery during spinal anesthesia: a pilot studyAnesth Analg9715011503PubMedCrossRefGoogle Scholar
  67. 67.
    Cowley, E, Thompson, JP, Sharpe, P, Waugh, J, Ali, N, Lambert, DG 2005Effects of pre-eclampsia on maternal plasma, cerebrospinal fluid, and umbilical cord urotensin II concentrations: a pilot studyBr J Anaesth95495499PubMedCrossRefGoogle Scholar
  68. 68.
    Balat, O, Aksoy, F, Kutlar, I, Ugur, MG, Iyikosker, H, Balat, A, Anarat, R 2005Increased plasma levels of urotensin-II in preeclampsia-eclampsia: a new mediator in pathogenesis?Eur J Obstet Gynecol Reprod Biol1203338PubMedCrossRefGoogle Scholar
  69. 69.
    Sondermeijer, B, Kompa, A, Komesaroff, P, Krum, H 2005Effect of exogenous urotensin-II on vascular tone in skin microcirculation of patients with essential hypertensionAm J Hypertens1811951199PubMedCrossRefGoogle Scholar
  70. 70.
    Totsune, K, Takahashi, K, Arihara, Z, Sone, M, Satoh, F, Ito, S, Kimura, Y, Sasano, H, Murakami, O 2001Role of urotensin II in patients on dialysisLancet358810811PubMedCrossRefGoogle Scholar
  71. 71.
    Totsune, K, Takahashi, K, Arihara, Z, Sone, M, Murakami, O, Ito, S, Kikuya, M, Ohkubo, T, Hashimoto, J, Imai, Y 2004Elevated plasma levels of immunoreactive urotensin II and its increased urinary excretion in patients with Type 2 diabetes mellitus: association with progress of diabetic nephropathyPeptides2518091814PubMedCrossRefGoogle Scholar
  72. 72.
    Wenyi, Z, Suzuki, S, Hirai, M, Hinokio, Y, Tanizawa, Y, Matsutani, A, Satoh, J, Oka, Y 2003Role of urotensin II gene in genetic susceptibility to Type 2 diabetes mellitus in Japanese subjectsDiabetologia46972976PubMedCrossRefGoogle Scholar
  73. 73.
    Suzuki, S, Wenyi, Z, Hirai, M, Hinokio, Y, Suzuki, C, Yamada, T, Yoshizumi, S, Suzuki, M, Tanizawa, Y, Matsutani, A, Oka, Y 2004Genetic variations at urotensin II and urotensin II receptor genes and risk of type 2 diabetes mellitus in JapanesePeptides2518031808PubMedCrossRefGoogle Scholar
  74. 74.
    Ong, KL, Wong, LY, Man, YB, Leung, RY, Song, YQ, Lam, KS, Cheung, BM 2006Haplotypes in the urotensin II gene and urotensin II receptor gene are associated with insulin resistance and impaired glucose tolerancePeptides2716591667PubMedCrossRefGoogle Scholar
  75. 75.
    Wilkinson, IB, Affolter, JT, de Haas, SL, Pellegrini, MP, Boyd, J, Winter, MJ, Balment, RJ, Webb, DJ 2002High plasma concentrations of human urotensin II do not alter local or systemic hemodynamics in manCardiovasc Res53341347PubMedCrossRefGoogle Scholar
  76. 76.
    Affolter, JT, Newby, DE, Wilkinson, IB, Winter, MJ, Balment, RJ, Webb, DJ 2002No effect on central or peripheral blood pressure of systemic urotensin II infusion in humansBr J Clin Pharmacol54617621PubMedCrossRefGoogle Scholar
  77. 77.
    Clozel, M, Hess, P, Qiu, C, Ding, SS, Rey, M 2006The urotensin-II receptor antagonist palosuran improves pancreatic and renal function in diabetic ratsJ Pharmacol Exp Ther31611151121PubMedCrossRefGoogle Scholar
  78. 78.
    Sidharta, PN, Wagner, FD, Bohnemeier, H, Jungnik, A, Halabi, A, Krahenbuhl, S, Chadha-Boreham, H, Dingemanse, J 2006Pharmacodynamics and pharmacokinetics of the urotensin II receptor antagonist palosuran in macroalbuminuric, diabetic patientsClin Pharmacol Ther80246256PubMedCrossRefGoogle Scholar
  79. 79.
    Grieco, P, Carotenuto, A, Campiglia, P, Zampelli, E, Patacchini, R, Maggi, CA, Novellino, E, Rovero, P 2002A new, potent urotensin II receptor peptide agonist containing a Pen residue at the disulfide bridgeJ Med Chem4543914394PubMedCrossRefGoogle Scholar
  80. 80.
    Behm, DJ, Stankus, G, Doe, CP, Willette, RN, Sarau, HM, Foley, JJ, Schmidt, DB, Nuthulaganti, P, Fornwald, JA, Ames, RS, Lambert, DG, Calo, G, Camarda, V, Aiyar, NV, Douglas, SA 2006The peptidic urotensin-II receptor ligand GSK248451 possesses less intrinsic activity than the low-efficacy partial agonists SB-710411 and urantide in native mammalian tissues and recombinant cell systemsBr J Pharmacol148173190PubMedCrossRefGoogle Scholar
  81. 81.
    Ng, LL, Loke, I, O'Brien, RJ, Squire, IB, Davies, JE 2002Plasma urotensin in human systolic heart failureCirculation10628772880PubMedCrossRefGoogle Scholar
  82. 82.
    Khan, SQ, Bhandari, SS, Quinn, P, Davies, JE, Ng, LL 2007Urotensin II is raised in acute myocardial infarction and low levels predict risk of adverse clinical outcome in humansInt J Cardiol117323328PubMedCrossRefGoogle Scholar
  83. 83.
    Dschietzig, T, Bartsch, C, Pregla, R, Zurbrugg, HR, Armbruster, FP, Richter, C, Laule, M, Romeyke, E, Neubert, C, Voelter, W, Baumann, G, Stangl, K 2002Plasma levels and cardiovascular gene expression of urotensin-II in human heart failureRegul Pept1103338PubMedCrossRefGoogle Scholar
  84. 84.
    Zhong, P, Li, ZL, Wu, HC, Tang, CS, Lu, Q 2003Clinical study of changes of urotensin II in patients with congestive heart failure (in Chinese)Di Yi Jun Yi Da Xue Xue Bao (Academic journal of the first medical college of PLA)23121123Google Scholar
  85. 85.
    Russell, FD, Meyers, D, Galbraith, AJ, Bett, N, Toth, I, Kearns, P, Molenaar, P 2003Elevated plasma levels of human urotensin-II immunoreactivity in congestive heart failureAm J Physiol Heart Circ Physiol285H15761581PubMedGoogle Scholar
  86. 86.
    Fang, SH, Li, ZL, Wu, HC, Tang, CS, Lu, Q, Liu, HC, Yan, QN 2004Clinical study of plasma urotensin II in patients with coronary heart disease (in Chinese)Di Yi Jun Yi Da Xue Xue Bao (Academic journal of the first medical college of PLA)24563565Google Scholar
  87. 87.
    Kruger, S, Graf, J, Kunz, D, Stickel, T, Merx, MW, Hanrath, P, Janssens, U 2005Urotensin II in patients with chronic heart failureEur J Heart Fail7475478PubMedCrossRefGoogle Scholar
  88. 88.
    Gruson, D, Rousseau, MF, Ahn, SA, van Linden, F, Ketelslegers, JM 2005Circulating urotensin II levels in moderate to severe congestive heart failure: its relations with myocardial function and well established neurohormonal markersPeptides2715271531PubMedCrossRefGoogle Scholar
  89. 89.
    Joyal, D, Huynh, T, Aiyar, N, Guida, B, Douglas, S, Giaid, A 2006Urotensin-II levels in acute coronary syndromesInt J Cardiol1083135PubMedCrossRefGoogle Scholar
  90. 90.
    Heringlake, M, Kox, T, Uzun, O, Will, B, Bahlmann, L, Klaus, S, Eleftheriadis, S, Armbruster, FP, Franz, N, Kraatz, E 2004The relationship between urotensin II plasma immunoreactivity and left ventricular filling pressures in coronary artery diseaseRegul Pept121129136PubMedCrossRefGoogle Scholar
  91. 91.
    Lapp, H, Boerrigter, G, Costello-Boerrigter, LC, Jaekel, K, Scheffold, T, Krakau, I, Schramm, M, Guelker, H, Stasch, J-P 2004Elevated plasma human urotensin-II-like immunoreactivity in ischemic cardiomyopathyInt J Cardiol949397PubMedCrossRefGoogle Scholar
  92. 92.
    Richards, AM, Nicholls, MG, Lainchbury, JG, Fisher, S, Yandle, TG 2002Plasma urotensin II in heart failureLancet360545546PubMedCrossRefGoogle Scholar
  93. 93.
    Simpson, CM, Penny, DJ, Stocker, CF, Shekerdemian, LS 2006Urotensin II is raised in children with congenital heart diseaseHeart92983984PubMedCrossRefGoogle Scholar
  94. 94.
    Cheung, BM, Leung, R, Man, YB, Wong, LY 2004Plasma concentration of urotensin II is raised in hypertensionJ Hypertens2213411344PubMedCrossRefGoogle Scholar
  95. 95.
    Balat, A, Pakir, IH, Gok, F, Anarat, R, Sahinoz, S 2005Urotensin-II levels in children with minimal change nephrotic syndromePediatr Nephrol204245PubMedCrossRefGoogle Scholar
  96. 96.
    Mallamaci, F, Cutrupi, S, Pizzini, P, Tripepi, G, Zoccali, C 2005Urotensin II in end-stage renal disease: an inverse correlate of sympathetic function and cardiac natriuretic peptidesJ Nephrol18727732PubMedGoogle Scholar
  97. 97.
    Zoccali, C, Mallamaci, F, Tripepi, G, Cutrupi, S, Pizzini, P, Malatino, L 2006Urotensin II is an inverse predictor of incident cardiovascular events in end-stage renal diseaseKidney Int6912531258PubMedCrossRefGoogle Scholar

Copyright information

© JSA 2007

Authors and Affiliations

  • John McDonald
    • 1
  • Madura Batuwangala
    • 1
  • David G. Lambert
    • 1
  1. 1.Department of Cardiovascular Sciences, Pharmacology and Therapeutics Group, Division of AnaesthesiaCritical Care and Pain Management, University of LeicesterLeicesterUK

Personalised recommendations