Differential effects of methanol on rat aortic smooth muscle.

The effects of methanol on isolated segments of rat aorta were investigated. In the absence of any vasoactive agent, methanol (5-675 mM) failed to alter basal tension. In rat aortic rings precontracted with high K+ (30 mM), methanol elicited a concentration-related relaxation at concentrations of from 5 to 675 mM. The K+-induced contraction in the presence of endothelium was more strongly inhibited by methanol than in the absence of endothelium. The effective concentration producing approximately 50% of the maximal relaxation response (ED50) to methanol was about 96 mM. Methanol-induced relaxations could not be abolished either by 5 x 10(-5) M N-nitro-L-arginine methyl ester (L-NAME) or NG-nitro-L-arginine (L-NNA), both selective inhibitors of nitric oxide (NO) formation; these relaxations were not potentiated by addition of excess L-arginine. An inhibitor of prostanoid synthesis, indomethacin (10(-5) M), had no effects on methanol-induced relaxation. Removal of extracellular Ca2+ ([Ca2+]o) resulted in almost complete inhibition of the relaxant effects of methanol on rat aortic ring segments. Marked attenuation of the relaxation responses of intact arteries to methanol was obtained after buffering intracellular Ca2+ ([Ca2+]i) with 10 microM BAPTA-AM. In 5-hydroxytryptamine (5-HT, 2.5 microM)- or phenylephrine (PE, 0.1 microM)-precontracted rat aortic rings, methanol amplified contractile responses to 5-HT and PE; these increased responses were concentration dependent. No significant differences in these methanol potentiated responses were found between aorta with or without endothelial cells. The amplified rat aortic smooth muscle responses induced by methanol after PE could be modified only by phentolamine, an antagonist of PE, while responses to 5-HT could be inhibited by methysergide (an antagonist of 5-HT) and by phentolamine, diphenhydramine, and haloperidol. Pretreatment with 50, 200, and 500 mM methanol increased rat aortic contractile responses induced by 5-HT and PE. Our results suggest that: (a) acute methanol exposure relaxes rat aortic smooth muscle contractile responses induced by high K+, leading to vessel relaxation. This relaxation effect of methanol is endothelium-dependent, clearly Ca2+ dependent, and independent of endogenous vasodilators such as acetylcholine, histamine, catecholamines, serotonin, or PG. (b) Methanol seems to increase potassium current by shifting the potential towards more negative values in depolarized vascular muscle cell membranes, probably inducing hyperpolarization of the cell membranes leading to a repolarization. (c) In contrast to the relaxant responses, methanol potentiates contractile response of rat aorta to 5-HT and PE.