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Endothelium‐Dependent Tolerance to Ethanol‐Induced Contraction of Rat Aorta: Effect of Inhibition of EDRF Action and Nitric Oxide Synthesis
Author(s) -
Knych Edward T.
Publication year - 1992
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1111/j.1530-0277.1992.tb00636.x
Subject(s) - nitric oxide , pyrogallol , chemistry , contraction (grammar) , nitroarginine , aorta , endothelium , carbachol , phenylephrine , endothelium derived relaxing factor , prostacyclin , pharmacology , nitric oxide synthase , in vitro , endocrinology , medicine , biochemistry , biology , receptor , organic chemistry , blood pressure
In vitro ethanol induces a dose‐dependent contraction of the aorta. Tolerance to this effect of ethanol is expressed by a rightward shift of the dose‐response curve in aorta from animals intoxicated with ethanol for 2 days. The expression of tolerance in the aorta is dependent upon the presence of functional endothelial cells which suggests that tolerance is mediated, in part, by endothelium‐derived relaxing factor (EDRF). To test this hypothesis, three inhibitors of EDRF action and an inhibitor of nitric oxide synthesis were studied for their ability to alter tolerance to ethanol‐induced contraction of the aorta. In vitro pretreatment of aortic rings with gossypol (10 ‐6 – 10 ‐5 M), pyrogallol (10 ‐5 M), hemoglobin (10 ‐6 M), and N G ‐nitro‐L‐arginine (NOARG, 10 ‐4 M) inhibited endothelium‐dependent relaxation induced by carbachol. The inhibition of carbachol‐induced relaxation produced by pyrogallol was reversed by superoxide dismutase (SOD, 45 units/ml). In vitro pretreatment of rings obtained from ethanol‐treated rats with gossypol, pyrogallol, hemoglobin, or NOARG inhibited the expression of ethanol tolerance, shifting the ethanol dose‐response curve to control values. SOD reversed the effect of pyrogallol pretreatment. None of the antagonists significantly altered the ethanol dose‐response curve of aortic rings obtained from control animals. These data support the hypothesis that tolerance to ethanol‐induced contraction of the aorta is mediated by the release of EDRF from endothelial cells.