Inhibition of myogenic tone by mibefradil in rat cerebral arteries.
The inhibitory effects of mibefradil (1.0 nM-1.0 microM), a putative selective inhibitor of T-type Ca2+ channels that has peripheral and coronary vasodilating properties with few negative inotropic effects, on pressure-induced vasoconstrictions were compared to depolarization- and [Arg8] vasopressin-induced tone in isolated middle cerebral arteries of the rat. The concentration-response relationships (IC50) for myogenic tone (70 +/- 20 nM), depolarization- (53 +/- 9 nM) and vasopressin-induced tone (70 +/- 10 nM) were equally inhibited by mibefradil. Pressure-induced responses were consistently inhibited by mibefradil throughout the myogenically active pressure range (20-100 mmHg). These results demonstrate that mibefradil is nonselective in inhibiting Ca2+ dependent cerebral artery tone due to myogenic activation, depolarization or receptor activation.
Lam
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E
Vancouver Vascular Biology Research Center, Department of Pharmacology and Therapeutics, Faculty of Medicine, The University of British Columbia, Canada.
Skarsgard
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P
Laher
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I
D000818:Animals; D001127:Arginine Vasopressin / Q000494:pharmacology; D001562:Benzimidazoles / Q000494:pharmacology*; D002536:Cerebral Arteries / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D008297:Male; D020748:Mibefradil; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D018006:Myogenic Regulatory Factors / Q000037:antagonists & inhibitors; D051381:Rats; D017207:Rats, Sprague-Dawley; D013764:Tetrahydronaphthalenes / Q000494:pharmacology*; D014662:Vasoconstrictor Agents / Q000494:pharmacology*; D014665:Vasodilator Agents / Q000494:pharmacology*
D001562:Benzimidazoles; D018006:Myogenic Regulatory Factors; D013764:Tetrahydronaphthalenes; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D001127:Arginine Vasopressin; D020748:Mibefradil