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
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