Urotensin-II: a novel systemic hypertensive factor in the cat

被引:32
作者
Behm, DJ [1 ]
Doe, CPA [1 ]
Johns, DG [1 ]
Maniscalco, K [1 ]
Stankus, GP [1 ]
Wibberley, A [1 ]
Willette, RN [1 ]
Douglas, SA [1 ]
机构
[1] GlaxoSmithKline, Cardiovasc & Urogenital Ctr Excellence Drug Disco, King Of Prussia, PA 19406 USA
关键词
urotensin-II; GPR14; UT; vasoconstriction; vascular resistance; blood pressure; hypertension; mesenteric arteries;
D O I
10.1007/s00210-004-0873-1
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
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 (pEC(50)s 9.68+/-0.24-8.73+/-0.08) and efficaciously (E-max 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.
引用
收藏
页码:274 / 280
页数:7
相关论文
共 33 条
[1]   No effect on central or peripheral blood pressure of systemic urotensin II infusion in humans [J].
Affolter, JT ;
Newby, DE ;
Wilkinson, IB ;
Winter, MJ ;
Balment, RJ ;
Webb, DJ .
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY, 2002, 54 (06) :617-621
[2]   Human urotensin-II is a potent vasoconstrictor and agonist for the orphan receptor GPR14 [J].
Ames, RS ;
Sarau, HM ;
Chambers, JK ;
Willette, RN ;
Alyar, NV ;
Romanic, AM ;
Louden, CS ;
Foley, JJ ;
Sauermelch, CF ;
Coatney, RW ;
Ao, ZH ;
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 .
NATURE, 1999, 401 (6750) :282-286
[3]  
[Anonymous], 1985, GUIDE CARE USE LAB A
[4]   Deletion of the UT receptor gene results in the selective loss of urotensin-II contractile activity in aortae isolated from UT receptor knockout mice [J].
Behm, DJ ;
Harrison, SM ;
Ao, ZH ;
Maniscalco, K ;
Pickering, SJ ;
Grau, EV ;
Woods, TN ;
Coatney, RW ;
Doe, CPA ;
Willette, RN ;
Johns, DG ;
Douglas, SA .
BRITISH JOURNAL OF PHARMACOLOGY, 2003, 139 (02) :464-472
[5]   Urotensin II evokes potent vasoconstriction in humans in vivo [J].
Böhm, F ;
Pernow, J .
BRITISH JOURNAL OF PHARMACOLOGY, 2002, 135 (01) :25-27
[6]   Human urotensin-II is an endothelium-dependent vasodilator in rat small arteries [J].
Bottrill, FE ;
Douglas, SA ;
Hiley, CR ;
White, R .
BRITISH JOURNAL OF PHARMACOLOGY, 2000, 130 (08) :1865-1870
[7]   Effects of human urotensin II in isolated vessels of various species;: comparison with other vasoactive agents [J].
Camarda, V ;
Rizzi, A ;
Calò, G ;
Gendron, G ;
Perron, SI ;
Kostenis, E ;
Zamboni, P ;
Mascoli, F ;
Regoli, D .
NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY, 2002, 365 (02) :141-149
[8]   Cloning, sequence analysis and tissue distribution of the mouse and rat urotensin II precursors [J].
Coulouarn, Y ;
Jégou, S ;
Tostivint, H ;
Vaudry, H ;
Lihrmann, I .
FEBS LETTERS, 1999, 457 (01) :28-32
[9]   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 [J].
Coulouarn, Y ;
Lihrmann, I ;
Jegou, S ;
Anouar, Y ;
Tostivint, H ;
Beauvillain, JC ;
Conlon, JM ;
Bern, HA ;
Vaudry, H .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1998, 95 (26) :15803-15808
[10]   Human urotensin-II as a novel cardiovascular target: 'heart' of the matter or simply a fishy 'tail'? [J].
Douglas, SA .
CURRENT OPINION IN PHARMACOLOGY, 2003, 3 (02) :159-167