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CARDIOVASCULAR

Ethanol Consumption Enhances Endothelin-1-Induced Contraction in the Isolated Rat Carotid

Department of Pharmacology, Faculty of Medicine of Ribeirão Preto (C.R.T.) and Department of Pharmacology, Institute of Biomedical Sciences (D.A.C., A.C.M., A.Y., R.C.T.), University of Sao Paulo, Sao Paulo, Sao Paulo, Brazil; Department of Pharmacology, Faculty of Medicine, Université de Sherbrooke, Sherbrooke, Québec, Canada (E.L., P.D.-J.); and Department of Clinical, Toxicological and Food Science Analysis (V.L.L., S.A.U.) and Department of Physics and Chemistry, Laboratory of Pharmacology (A.M.d.O.), Faculty of Pharmaceutical Sciences, University of Sao Paulo, Ribeirão Preto, Sao Paulo, Brazil

We investigated the mechanisms involved in the enhancement of endothelin (ET)-1 vascular reactivity induced by ethanol consumption. Ethanol intake for 2, 6, and 10 weeks enhanced the ET-1-induced contractile response of endothelium-intact but not endothelium-denuded rat carotid rings independently of the treatment duration. Conversely, phenylephrine-induced contraction was not affected by ethanol intake. The contraction induced by IRL1620 [succinyl-(Glu⁹,Ala^11,15)-ET-1-(8-21)], a selective ET_B agonist, was increased after treatment with ethanol in endothelium-intact but not in endothelium-denuded carotid rings. Moreover, ET-1- and IRL1620-induced relaxation was reduced in endothelium-intact phenylephrine-precontracted rings from ethanol-treated rats. Acetylcholine-induced relaxation was not affected by ethanol treatment. N^G-Nitro-L-arginine methyl ester, 1H-[1,2,4]-oxadiazolo[4,3-a]quinoxalin-1-one, indomethacin, and tetraethylammonium reduced the relaxation induced by IRL1620 in carotid glands from control but not ethanol-treated rats. The mRNA levels for ET_A and ET_B receptors were not altered by ethanol consumption. However, ethanol treatment reduced the protein expression of ET_B receptors. Furthermore, immunohistochemical assays showed reduced immunostaining for endothelial ET_B receptors after treatment with ethanol. We conclude that ethanol consumption enhances ET-1-induced contraction in the rat carotid and that this response is not different among the three periods of treatment used in this study. Finally, the potentiation of ET-1-induced vascular reactivity is probably caused by reduced expression of relaxing endothelial ET_B receptors.

Address correspondence to: Dr. Ana Maria de Oliveira, Universidade de Sao Paulo, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Avenida do Café s/n, CEP 14040-903, Ribeirão Preto, Sao Paulo, Brazil. E-mail: amolive{at}usp.br

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