title: Effect of chronic ethanol consumption on endothelin-1 generation and conversion of exogenous big-endothelin-1 by the rat carotid artery.
abstract: The purpose of the present work was to investigate whether conversion of exogenous applied big-endothelin-1 (Big-ET-1) as well as the basal release and mRNA levels of endothelin-1 (ET-1) is altered by ethanol consumption in the rat carotid. The measurement of the contraction induced by Big-ET-1 served as an indicative of functional endothelin (ET)-converting enzyme (ECE) activity. Cumulative application of exogenous Big-ET-1 elicited a concentration-related contraction with the concentration-response curve shifted to the right when compared to ET-1. In endothelium-intact rings, phosphoramidon (1 mmol/l), a nonselective ECE/neutral endopeptidase (NEP) inhibitor, produced a rightward displacement of the concentration-response curves and reduced the maximal contractile response to Big-ET-1. However, in endothelium-denuded rings phosphoramidon reduced the maximum contraction for Big-ET-1 but did not alter the potency when compared to the curves obtained in the absence of the inhibitor. Ethanol consumption for 2, 6, or 10 weeks reduced the contractile effect elicited by Big-ET-1 in carotid rings with intact endothelium when compared to control or isocaloric rings. However, no differences on Big-ET-1-induced contraction were observed after endothelial denudation. On the other hand, ethanol consumption increased ET-1-induced contraction. Finally, chronic ethanol consumption did not alter either the mRNA levels for pre-pro-ET-1 nor the basal release of ET-1. The present findings show that chronic ethanol consumption does not alter the mRNA levels for ET-1 or its basal release in the rat carotid. Moreover, ethanol intake reduces the contraction induced by exogenously applied Big-ET-1 in carotid rings with intact endothelium, a fact that might be the result of a reduced conversion of this peptide by ECE on its mature active peptide ET-1.
authors.affiliation: Department of Psychiatry Nursing and Human Sciences, College of Nursing of Ribeirão Preto, University of São Paulo (USP), SP, Brazil.
authors.forename: Carlos R
authors.initials: CR
authors.lastname: Tirapelli
authors.forename: Débora A
authors.initials: DA
authors.lastname: Casolari
authors.forename: Alvaro
authors.initials: A
authors.lastname: Yogi
authors.forename: Rita C
authors.initials: RC
authors.lastname: Tostes
authors.forename: Eurode
authors.initials: E
authors.lastname: Legros
authors.forename: Vera L
authors.initials: VL
authors.lastname: Lanchote
authors.forename: Sérgio A
authors.initials: SA
authors.lastname: Uyemura
authors.forename: Ana M
authors.initials: AM
authors.lastname: de Oliveira
mesh_terms: D000428:Alcohol Drinking / Q000378:metabolism / Q000503:physiopathology*; D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D002339:Carotid Arteries / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D002492:Central Nervous System Depressants / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D019332:Endothelin-1 / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D000072396:Endothelin-Converting Enzymes; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D000431:Ethanol / Q000008:administration & dosage / Q000494:pharmacology*; D006020:Glycopeptides / Q000494:pharmacology; D008297:Male; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011480:Protease Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D014661:Vasoconstriction / Q000187:drug effects*
chemical_list: D002492:Central Nervous System Depressants; D019332:Endothelin-1; D006020:Glycopeptides; D011480:Protease Inhibitors; D012333:RNA, Messenger; D000431:Ethanol; D016282:Aspartic Acid Endopeptidases; D008666:Metalloendopeptidases; D000072396:Endothelin-Converting Enzymes; C008890:phosphoramidon