ETHANOL ENHANCES THE ENDOTHELIAL NITRIC-OXIDE SYNTHASE RESPONSE TO AGONISTS

Chronic ethanol consumption is associated with an increased prevalence of hypertension. The mechanisms of this form of hypertension are unkn own. Rats fed ethanol for 2 days develop a tolerance to the acute vaso constrictive effects of ethanol that is believed to be endothelium dep endent. We investigated the effects of acute and chronic ethanol expos ure on agonist-stimulated nitric oxide synthase activity in bovine pul monary artery endothelial cells. Exposure of bovine pulmonary artery e ndothelial cells to ethanol (100 mmol/L) for 20-120 minutes did not ch ange either basal or agonist-stimulated nitric oxide synthase activity measured as the rate of conversion of [H-3]L-arginine to [H-3]L-citru lline. Chronic exposure of endothelial cells to ethanol (100 mmol/L) f or 96 hours significantly increased bradykinin-, adenosine 5'-triphosp hate-, and ionomycin-stimulated nitric oxide synthase activity without affecting basal enzyme activity. The ethanol-induced increase in nitr ic oxide synthase response to agonists was dependent on the duration o f ethanol exposure as well as the concentration of ethanol. Moreover, the effect of ethanol was characterized by an increase in the maximal nitric oxide synthase response to adenosine 5'-triphosphate without ch anges in the EC50. Removal of calcium or addition of N-nitro-L-arginin e completely abolished agonist-stimulated nitric oxide synthase activi ty in both control and ethanol-treated cells. Our observations support the hypothesis that ethanol enhances nitric oxide synthase response t o agonists during early ethanol exposure and may serve in a protective role against its hypertensive effect.