Acute and chronic effects of ethanol and its metabolites on vascular production of prostacyclin in rats.
The cutaneous vasodilation produced by ethanol is exaggerated when acetaldehyde levels are increased after aldehyde dehydrogenase inhibition, producing a flushing reaction, the mechanism of which is unknown. The authors investigated whether ethanol and its metabolites affect the vascular release of prostacyclin, a potent vasodilator, and whether such an effect might be modified by chronic alcohol consumption. Aortic rings from rats fed Chow ad libitum or pair-fed liquid diets containing either ethanol (36% of energy) or isocaloric carbohydrate for 4 to 5 weeks were incubated in Krebs-Ringer bicarbonate supplemented with saturating amounts of arachidonate (10-20 microM) in the presence of ethanol (10-100 mM), acetaldehyde (10-100 microM) or acetate (1.25-5 mM). Prostacyclin was measured by the radioimmunoassay of 6-keto-prostaglandin F1 alpha. Acetaldehyde produced a concentration-dependent stimulation of prostacyclin production both in alcohol-fed and control rats, whereas acetate did not. This effect was associated with increased conversion of arachidonate (either exogenous or released with A23187) and of prostaglandin endoperoxide H2 to prostacyclin. Ethanol did not affect prostacyclin release in control rats, but, in aortas from alcohol-fed animals, 50 mM ethanol did stimulate prostacyclin formation. These effects may contribute to the cardiovascular responses associated with high blood acetaldehyde levels in flushers and with high ethanol levels in alcoholics. In conclusion, acetaldehyde is a potent stimulant of vascular prostacyclin production. This effect is due, at least in part, to enhanced activity of prostacyclin synthase. Ethanol acquires such a stimulatory effect on prostacyclin formation after chronic alcohol consumption.
D000079:Acetaldehyde / Q000494:pharmacology*; D000085:Acetates / Q000494:pharmacology*; D019342:Acetic Acid; D000426:Alcohol Dehydrogenase / Q000378:metabolism; D000437:Alcoholism / Q000378:metabolism*; D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism; D000001:Calcimycin / Q000494:pharmacology; D004040:Dietary Carbohydrates / Q000494:pharmacology; D011464:Epoprostenol / Q000096:biosynthesis*; D000431:Ethanol / Q000494:pharmacology*; D008297:Male; D011450:Prostaglandin Endoperoxides, Synthetic / Q000378:metabolism; D044262:Prostaglandin H2; D011463:Prostaglandins H / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D014664:Vasodilation / Q000187:drug effects
D000085:Acetates; D001095:Arachidonic Acids; D004040:Dietary Carbohydrates; D011450:Prostaglandin Endoperoxides, Synthetic; D011463:Prostaglandins H; D016718:Arachidonic Acid; D000001:Calcimycin; D000431:Ethanol; D044262:Prostaglandin H2; D011464:Epoprostenol; D000426:Alcohol Dehydrogenase; D000079:Acetaldehyde; D019342:Acetic Acid