The Role of Endothelium in Tolerance to Ethanol‐Induced Contraction of the Rat Aorta

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Abstract
After 2 days of intoxication an endothelium‐dependent tolerance to ethanol‐induced contraction of the rat aorta develops. This study investigates the possibility that the observed tolerance may be due to the recently described endothelium‐dependent vasodilator system which mediates the action of several potent vasodilators. The maximum response induced by ethanol in control and intoxicated aortic rings with endothelium was significantly increased by treatment with eicosatetraynoic acid and methylene blue. In addition, these agents significantly decreased the EC50 of ethanol in intoxicated but not control rings with endothelium. The response of control and intoxicated aortic rings without endothelium was unaltered by eicosatetraynoic acid or methylene blue. Indomethacin, nordihydroguaiaretic acid, and FPL 55712 did not alter either the maximum response or the EC50 of ethanol in control or intoxicated rings with endothelium. These observations support the hypothesis that the endothelium‐dependent tolerance observed in the aorta may be due to the release of an endothelium‐derived relaxing factor.