Ethanol enhances the endothelial nitric oxide synthase response to agonists.

Abstract

Chronic ethanol consumption is associated with an increased prevalence of hypertension. The mechanisms of this form of hypertension are unknown. Rats fed ethanol for 2 days develop a tolerance to the acute vasoconstrictive effects of ethanol that is believed to be endothelium dependent. We investigated the effects of acute and chronic ethanol exposure on agonist-stimulated nitric oxide synthase activity in bovine pulmonary artery endothelial cells. Exposure of bovine pulmonary artery endothelial cells to ethanol (100 mmol/L) for 20-120 minutes did not change either basal or agonist-stimulated nitric oxide synthase activity measured as the rate of conversion of [Chronic exposure of endothelial cells to ethanol (100 mmol/L) for 96 hours significantly increased bradykinin-, adenosine 5'-triphosphate-, and ionomycin-stimulated nitric oxide synthase activity without affecting basal enzyme activity. The ethanol-induced increase in nitric oxide synthase response to agonists was dependent on the duration of 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 changes in the EC^. Removal of calcium or addition of iV-nitro-L-arginine completely abolished agonist-stimulated nitric oxide synthase activity in both control and ethanol-treated cells. Our observations support the hypothesis that ethanol enhances nitric oxide synthase response to agonists during early ethanol exposure and may serve in a protective role against its hypertensive effect (Hypertension 1993^1:939-943) KEY WORDS • ethanol • endothelium • nitric oxide • endothelium-derived relaxing factor • hypertension, ethanol-related C hronic ethanol (EtOH) consumption is associated with an increased prevalence of arterial hypertension in humans and experimental animals.'" 3 The mechanisms of ethanol-associated hypertension are unknown but may include intermittent withdrawal, alterations in catecholamine production, and direct constrictive effects of ethanol on blood vessels.1 In animal and human studies, the acute administration of ethanol results in vasoconstriction of most vascular beds. 4 -3 However, chronic ethanol feeding to rats results in the early development of tolerance to the acute vasoconstrictive effect of ethanol 6 -7 that is believed to be endothelium dependent. 89 In addition, studies in ethanol-fed rats have demonstrated augmented relaxation of vascular rings to acetylcholine and adenosine 5'-triphosphate (ATP).

Autocrine inhibition of Na+/K(+)-ATPase by nitric oxide in mouse proximal tubule epithelial cells.

“…3). This assay is very sensitive for measuring NOS activity (17,21,22). Thus, these studies demonstrate a close correlation between the time course of iNOS induction and the inhibition of Na +/K + -ATPase activity.…”

HDL-associated estradiol stimulates endothelial NO synthase and vasodilation in an SR-BI–dependent manner

“…NOS activation was determined in intact cells as previously described (21,30). Briefly, the cells were plated into 12-well plates at 5,000 cells per well and grown to 60% confluency.…”

Ethanol inhibits monocyte chemotactic protein-1 expression in interleukin-1β-activated human endothelial cells

“…However, the precise cellular mechanisms whereby ethanol (EtOH) elicits its cardioprotective effects are not yet fully understood. In addition to favorable effects on plasma lipoprotein levels, potentially beneficial effects of EtOH on platelets and on vascular endothelial cells and smooth muscle cells (SMC) have been recently reported (6,10,11,24,26).Monocyte chemotactic protein-1 (MCP-1) is a member of the C-C chemokine family and a potent chemoattractant for monocytes (27). The involvement of MCP-1 in the pathogenesis of atherosclerosis has been widely investigated, and much evidence exists to support its central role in the process.…”

“…However, the precise cellular mechanisms whereby ethanol (EtOH) elicits its cardioprotective effects are not yet fully understood. In addition to favorable effects on plasma lipoprotein levels, potentially beneficial effects of EtOH on platelets and on vascular endothelial cells and smooth muscle cells (SMC) have been recently reported (6,10,11,24,26).…”