Ethanol inhibits intra- and extracellular Ca(2+)-dependent contraction of rat aorta by different mechanisms.
The mechanism of the inhibitory action of ethanol on vasoconstriction was studied by examining ethanol effects on vascular responses to different vasoconstrictive stimulants using isolated rat aorta. Ethanol pretreatment of aortic strips at 200 and 400 mM significantly inhibited contractile responses to KCl and 5-hydroxytryptamine in the standard medium. This inhibitory effect on vasoconstriction was observed whether or not the endothelium was present. Pretreatment with ethanol (400 mM) caused significant decrease of 45Ca2+ uptake induced by KCl when compared to the control. This pretreatment also significantly inhibited the contractile response to 5-hydroxytryptamine in the medium without Ca2+, decreased 5-hydroxytryptamine-stimulated inositol monophosphate accumulation, and significantly inhibited a transient contraction induced by 20 mM caffeine. Ethanol (400 mM) inhibited phorbol 12, 13-dibutyrate (PDBu)-induced contraction when Ca2+ was present in medium, but not when it was absent. These results suggest that ethanol acts on different sites of the signal transduction pathway of rat aortic smooth muscle, causing inhibition of transmembraneous Ca2+ influx through voltage-dependent Ca2+ channels, phosphoinositide hydrolysis and Ca(2+)-induced Ca2+ release. However, the cytoskeletal contractile apparatus may remain intact after ethanol treatment.
Department of Hygiene and Preventive Medicine, School of Medicine, Yamagata University, Japan.
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Wakabayashi
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Hatake
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Hishida
D000818:Animals; D001011:Aorta / Q000187:drug effects*; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism; D000431:Ethanol / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D010716:Phosphatidylinositols / Q000378:metabolism; D011189:Potassium Chloride / Q000037:antagonists & inhibitors; D051381:Rats; D017208:Rats, Wistar; D012702:Serotonin Antagonists; D015398:Signal Transduction / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects*
D015220:Calcium Channels; D010716:Phosphatidylinositols; D012702:Serotonin Antagonists; D015240:Phorbol 12,13-Dibutyrate; D000431:Ethanol; D011189:Potassium Chloride; D002118:Calcium