Methanol-induced contraction of canine cerebral artery and its possible mechanism of action.

In the present report, we investigated the effects of methanol on canine basilar cerebral arterial rings. Our data indicate that acute methanol exposure (5-675 mM) induces potent contractile responses of cerebral arteries in a concentration-dependent manner. Pharmacological antagonists, such as propranolol, phentolamine, haloperidol, methysergide, naloxone, diphenhydramine, and cimetidine, did not exert any effects on these methanol-induced contractions. Likewise, a potent antagonist of cyclo-oxygenase, and subsequent synthesis of prostanoids (i.e., indomethacin), failed to exert any effect on methanol-induced contractions. No differences in responsiveness to methanol in canine cerebral arteries were found in vessel segments with or without endothelial cells. Removal of extracellular Ca2+ ([Ca2+]o) partially attenuated methanol-induced contractions, while withdrawal of extracellular Mg2+ ([Mg2+]o) potentiated the contractions. In the complete absence of [Ca2+]o, 10 mM caffeine and 400 mM methanol induced similar, transient contractions followed by relaxation in K(+)-depolarized cerebral vascular tissues. Methanol-induced contractions were, however, completely abolished by pretreatment of tissue with 10 mM caffeine. Our results indicate that (1) methanol causes contractile responses of cerebral arterial smooth muscle (independent of amine, prostanoid, or opioid mediation; (2) in addition to a need for [Ca2+]o, an intracellular release of Ca2+ is required for methanol-induced contractions; and (3) Mg deficiency potentiates the contractile responses of methanol on these brain vessels. The data presented in the study suggest that methanol-induced contractions occur via an sarcoplasmic reticulum-releasable store of [Ca2+]i; via mediation of either ryanodine-caffeine type receptors or a caffeine-releasable intracellular store of CA2+.