title: Ethanol consumption enhances endothelin-1-induced contraction in the isolated rat carotid.
abstract: 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-(Glu(9),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.
authors.affiliation: Department of Pharmacology, Faculty of Medicine of Ribeirão Preto, University of Sao Paulo, Sao Paulo, Sao Paulo, Brazil.
authors.forename: Carlos R
authors.initials: CR
authors.lastname: Tirapelli
authors.forename: Débora A
authors.initials: DA
authors.lastname: Casolari
authors.forename: Augusto C
authors.initials: AC
authors.lastname: Montezano
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: Pedro
authors.initials: P
authors.lastname: D'Orléans-Juste
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: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D015153:Blotting, Western; D001835:Body Weight / Q000187:drug effects; D002339:Carotid Arteries / Q000187:drug effects*; D002492:Central Nervous System Depressants / Q000097:blood / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D019332:Endothelin-1 / Q000494:pharmacology*; D016232:Endothelins / Q000494:pharmacology; D000431:Ethanol / Q000097:blood / Q000494:pharmacology*; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009842:Oligopeptides / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D044022:Receptor, Endothelin A / Q000096:biosynthesis; D044023:Receptor, Endothelin B / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D001786:Blood Glucose; D002492:Central Nervous System Depressants; D019332:Endothelin-1; D016232:Endothelins; D009842:Oligopeptides; D010446:Peptide Fragments; D010456:Peptides, Cyclic; D010880:Piperidines; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; C074308:sovateltide; D010656:Phenylephrine; D000431:Ethanol; C086539:BQ 788; D000109:Acetylcholine; C072247:cyclo(Trp-Asp-Pro-Val-Leu)