Abstract
Urotensin-II, a potent mammalian vasoconstrictor, may play a role in the etiology of essential hypertension. However, a species suitable for assessing such a role, one where a “classical” systemic hypertensive response (increase in mean blood pressure and systemic vascular resistance) is observed following bolus i.v. urotensin-II administration, has yet to be identified. The present study demonstrates that the cat may represent such a species since urotensin-II potently (pEC50s 9.68±0.24–8.73±0.08) and efficaciously (Emax 73±15%–205±21% KCl) constricts all feline isolated arteries studied (aortae, renal, femoral, carotid, and mesenteric conduit/resistance). Accordingly, exogenous urotensin-II (1 nmol/kg, i.v.) effectively doubles both mean blood pressure (from 99±14 to 183±15 mmHg) and systemic vascular resistance (from 0.36±0.12 to 0.86±0.20 mmHg/ml/min) in the anaesthetized cat (without altering heart rate or stroke volume). Thus, in view of these profound contractile effects, the cat could be suitable for determining the effects of urotensin-II receptor antagonism on cardiovascular homeostasis in both normal and diseased states.
Similar content being viewed by others
References
Affolter JT, Newby DE, Wilkinson IB, Winter MJ, Balment RJ, Webb DJ (2002) No effect on central or peripheral blood pressure of systemic urotensin II infusion in humans. Br J Clin Pharmacol 54:617–621
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 DWP, Ohlstein EH, Bergsma DJ, Douglas SA (1999) Human urotensin-II is a potent vasoconstrictor and agonist for the orphan receptor GPR14. Nature 401:282–286
Behm DJ, Harrison SM, Ao Z, Maniscalco K, Pickering SJ, Grau EV, Woods TN, Coatney RW, Doe CPA, Willette RN, Johns DG, Douglas SA (2003) 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 139:464–472
Böhm F, Pernow J (2002) Urotensin II evokes potent vasoconstriction in humans in vivo. Br J Pharmacol 135:25–27
Bottrill FE, Douglas SA, Hiley CR, White R (2000) Human urotensin-II is an endothelium-dependent vasodilator in rat small arteries. Br J Pharmacol 130:1865–1870
Camarda V, Rizzi A, Calo G, Gendron G, Perron SI, Kostenis E, Zamboni P, Mascoli F, 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
Coulouarn Y, Lihrmann I, Jegou S, Anouar Y, Tostivint H, Beauvillain JC, Conlon JM, Bern HA, Vaudry H (1998) 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 95:15803–15808
Coulouarn Y, Jegou S, Tostivint H, Vaudry H, Lihrmann I (1999) Cloning sequence analysis and tissue distribution of the mouse and rat urotensin II precursors. FEBS Lett 457:28–32
Douglas SA (2003) Human urotensin-II as a novel cardiovascular target: ‘heart’ of the matter or simply a fishy ‘tail’. Curr Opin Pharmacol 3:159–167
Douglas SA, Ohlstein EH (2000) Urotensin receptors. In: Girdlestone D (ed) The IUPHAR compendium of receptor characterization and classification. IUPHAR Media, London, pp 365–372
Douglas SA, Sulpizio AC, Piercy V, Sarau HM, Ames RS, Aiyar NV, Ohlstein EH, Willette RN (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
Douglas SA, Tayara L, Ohlstein EH, Halawa N, Giaid A (2002) Congestive heart failure and expression of myocardial urotensin II. Lancet 359:1990–1997
Elshourbagy NA, Douglas SA, Shabon U, Harrison S, Duddy G, Sechler JL, Ao Z, Maleeff BE, Naselsky D, Disa J, Aiyar NV (2002) Molecular and pharmacological characterization of genes encoding urotensin-II peptides and their cognate G-protein-coupled receptors from the mouse and monkey. Br J Pharmacol 136:9–22
Gardiner SM, March JE, Kemp PA, Davenport AP, Bennett T (2001) Depressor and regionally-selective vasodilator effects of human and rat urotensin II in conscious rats. Br J Pharmacol 132:1625–1629
Horie S, Yasuda S, Tsurumaki Y, Someya A, Saito T, Okuma Y, Nomura Y, Hirabayashi T, Murayama T (2003) Contractions of isolated guinea-pig ileum by urotensin II via activation of ganglionic cholinergic neurons and acetylcholine release. Neuropharmacology 45:1019–1027
Leslie SJ, Denvir M, Webb DJ (2000) Human urotensin-II causes vasoconstriction in the human skin microcirculation. Circulation 102:II–113
Lin Y, Tsuchihashi T, Matsumura K, Abe I, Iida M (2003) Central cardiovascular action of urotensin II in conscious rats. J Hypertens 21:159–165
MacLean MR, Alexander D, Stirrat A, Gallagher M, Douglas SA, Ohlstein EH, Morecroft I, 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
Maguire JJ, Kuc RE, Davenport AP (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
Matsushita M, Shichiri M, Imai T, Iwashina M, Tanaka H, Takasu N, Hirata Y (2001) Co-expression of urotensin II and its receptor (GPR14) in human cardiovascular and renal tissues. J Hypertens 19:2185–2190
Mulvany MJ, Halpern W (1977) Contractile properties of small arterial resistance vessels in spontaneously hypertensive and normotensive rats. Circ Res 41:19–26
National Institute of Health (1985) Principles of laboratory animal care. NIH publication No. 85–23, revised edn. National Institute of Health
National Research Council (1996) Guide for the care and use of laboratory animals. Institute of Laboratory Animal Resources, National Research Council
Paysant J, Rupin A, Simonet S, Fabiani JN, Verbeuren TJ (2001) Comparison of the contractile responses of human coronary bypass grafts and monkey arteries to human urotensin-II. Fundam Clin Pharmacol 15:227–231
Pearson D, Shively JE, Clark BR, Geschwind II, Barkley M, Nishioka RS, Bern HA (1980) Urotensin II: a somatostatin-like peptide in the caudal neurosecretory system of fishes. Proc Natl Acad Sci USA 77:5021–5024
Richards AM, Nicholls MG, Lainchbury JG, Fisher S, Yandle TG (2002) Plasma urotensin II in heart failure. Lancet 360:545–546
Russell FD, Molenaar P, O’Brien DM (2001) Cardiostimulant effects of urotensin-II in human heart in vitro. Br J Pharmacol 132:5–9
Saetrum Opgaard O, Nothacker H, Ehlert FJ, Krause DN (2000) Human urotensin II mediates vasoconstriction via an increase in inositol phosphates. Eur J Pharmacol 406:265–271
Stirrat A, Gallagher M, Douglas SA, Ohlstein EH, Berry C, Kirk A, Richardson M, MacLean MR (2001) Potent vasodilator responses to human urotensin-II in human pulmonary and abdominal resistance arteries. Am J Physiol Heart Circ Physiol 280:H925–928
Thompson JP, Watt P, Sanghavi S, Strupish JW, Lamber DG (2003) 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 97:1501–1503
Watson AM, Lambert GW, Smith KJ, May C.N (2003) Urotensin II acts centrally to increase epinephrine and ACTH release and cause potent inotropic and chronotropic actions. Hypertension 42:373–379
Wilkinson IB, Affolter JT, de Haas SL, Pellegrini MP, Boyd J, Winter MJ, Balment RJ, Webb DJ (2002) High plasma concentrations of human urotensin II do not alter local or systemic haemodynamics in man. Cardiovasc Res 53:341–347
Zhang AY, Chen YF, Zhang DX, Yi FX, Qi J, Andrade-Gordon P, de Garavilla L, Li PL, Zou AP (2003) Urotensin II is a nitric oxide-dependent vasodilator and natriuretic peptide in the rat kidney. Am J Physiol 285:F792–798
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Behm, D.J., Doe, C.P.A., Johns, D.G. et al. Urotensin-II: a novel systemic hypertensive factor in the cat. Naunyn-Schmiedeberg's Arch Pharmacol 369, 274–280 (2004). https://doi.org/10.1007/s00210-004-0873-1
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00210-004-0873-1