Urotensin-II: a novel systemic hypertensive factor in the cat.
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.
Behm
David J
DJ
Cardiovascular and Urogenital Center of Excellence for Drug Discovery, GlaxoSmithKline, 709 Swedeland Road, King of Prussia, PA 19406-0939, USA. David_J_Behm@gsk.com
Doe
Christopher P A
CP
Johns
Douglas G
DG
Maniscalco
Kristeen
K
Stankus
Gerald P
GP
Wibberley
Alexandra
A
Willette
Robert N
RN
Douglas
Stephen A
SA
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D002415:Cats; D004305:Dose-Response Relationship, Drug; D006801:Humans; D006973:Hypertension / Q000139:chemically induced* / Q000503:physiopathology; D066298:In Vitro Techniques; D008297:Male; D014579:Urotensins / Q000494:pharmacology* / Q000633:toxicity; D014661:Vasoconstriction / Q000187:drug effects* / Q000502:physiology
D014579:Urotensins; C029677:urotensin II