共 33 条
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.
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页码:274 / 280
页数:7
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