Inhibition of myogenic tone by mibefradil in rat cerebral arteries

Eur J Pharmacol. 1998 Oct 2;358(2):165-8. doi: 10.1016/s0014-2999(98)00611-6.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arginine Vasopressin / pharmacology
  • Benzimidazoles / pharmacology*
  • Cerebral Arteries / drug effects
  • Dose-Response Relationship, Drug
  • Male
  • Mibefradil
  • Muscle, Smooth, Vascular / drug effects*
  • Myogenic Regulatory Factors / antagonists & inhibitors
  • Rats
  • Rats, Sprague-Dawley
  • Tetrahydronaphthalenes / pharmacology*
  • Vasoconstrictor Agents / pharmacology*
  • Vasodilator Agents / pharmacology*

Substances

  • Benzimidazoles
  • Myogenic Regulatory Factors
  • Tetrahydronaphthalenes
  • Vasoconstrictor Agents
  • Vasodilator Agents
  • Arginine Vasopressin
  • Mibefradil