Urotensin-II: a novel systemic hypertensive factor in the cat |
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Authors: | David J. Behm Christopher P. A. Doe Douglas G. Johns Kristeen Maniscalco Gerald P. Stankus Alexandra Wibberley Robert N. Willette Stephen A. Douglas |
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Affiliation: | (1) Cardiovascular and Urogenital Center of Excellence for Drug Discovery, GlaxoSmithKline, 709 Swedeland Road, King of Prussia, PA 19406–0939, USA |
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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. |
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Keywords: | Urotensin-II GPR14 UT Vasoconstriction Vascular resistance Blood pressure Hypertension Mesenteric arteries |
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