METHANOL-INDUCED CONTRACTION OF CANINE CEREBRAL-ARTERY AND ITS POSSIBLE MECHANISM OF ACTION

In the present report, we investigated the effects of methanol on cani ne basilar cerebral arterial rings. Our data indicate that acute metha nol exposure (5-675 mM) induces potent contractile responses of cerebr al arteries in a concentration-dependent manner. Pharmacological antag onists, such as propranolol, phentolamine, haloperidol, methysergide, naloxone, diphenhydramine, and cimetidine, did not exert any effects o n these methanol-induced contractions. Likewise, a potent antagonist o f cyclo-oxygenase, and subsequent synthesis of prostanoids (i.e., indo methacin), failed to exert any effect on methanol-induced contractions . No differences in responsiveness to methanol in canine cerebral arte ries were found in vessel segments with or without endothelial cells. Removal of extracellular Ca2+ ([Ca2+],) partially attenuated methanol- induced contractions, while withdrawal of extracellular Mg2+ ([Mg2+],) potentiated the contractions. In the complete absence of [Ca2+](o), 1 0 mM caffeine and 400 mM methanol induced similar, transient contracti ons 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 pot entiates the contractile responses of methanol on these brain vessels. The data presented in the study suggest that methanol-induced contrac tions occur via an sarcoplasmic reticulum-releasable store of [Ca2+](i ); via mediation of either ryanodine-caffeine type receptors or a caff eine-releasable intracellular store of Ca2+. (C) 1998 Academic Press.