Chronic Ethanol Consumption Enhances Phenylephrine-Induced Contraction in the Isolated Rat Aorta

• Published in: The Journal of pharmacology and experimental therapeutics Vol. 316; no. 1; pp. 233 - 241
• Main Authors: Tirapelli, Carlos R, Al-Khoury, Johny, Bkaily, Ghassan, D'Orléans-Juste, Pedro, Lanchote, Vera L, Uyemura, Sergio A, de Oliveira, Ana M
• Format: Journal Article
• Language: English
• Published: United States American Society for Pharmacology and Experimental Therapeutics 01.01.2006
• Subjects: Animals; Aorta, Thoracic - drug effects; Arachidonic Acid - metabolism; Arachidonic Acid - physiology; Blood Glucose - metabolism; Body Weight - drug effects; Calcium - metabolism; Cardiotonic Agents - pharmacology; Central Nervous System Depressants - blood; Central Nervous System Depressants - pharmacology; Cytosol - drug effects; Cytosol - metabolism; Dose-Response Relationship, Drug; Endothelin-1 - pharmacology; Endothelium, Vascular - enzymology; Endothelium, Vascular - physiology; Ethanol - blood; Ethanol - pharmacology; Heart - drug effects; Male; Muscle Contraction - drug effects; Muscle, Smooth, Vascular - drug effects; Nitric Oxide - physiology; Phenylephrine - pharmacology; Prostaglandin-Endoperoxide Synthases - metabolism; Rats; Rats, Wistar; Thromboxane A2 - metabolism
• ISSN: 0022-3565; 1521-0103
• DOI: 10.1124/jpet.105.092999

Changes in reactivity to phenylephrine in aortas isolated from 2-, 6-, and 10-week ethanol-treated rats and their age-matched control and isocaloric rats were investigated. Chronic ethanol consumption enhances the contractile response of endothelium-intact and -denuded rat aortic rings to phenylephrine, a response that is time-independent. Pretreatment with indomethacin reduced E max for phenylephrine in denuded aortas from ethanol-treated rats but not control or isocaloric rats. After indomethacin treatment, no differences in E max from phenylephrine were observed among the groups. SQ29548 ([1 S -[1α-2α( Z )3α,4α]]-7-[3-[[(phenylamino)carbonyl]hydrazino]methyl]-7-oxabicyclo[2.2.1]hept-2-yl]-5-heptenoic acid), an antagonist of prostaglandin H 2 /thromboxane A 2 (TXA 2 ) receptors, did not alter phenylephrine-induced contraction in control or isocaloric aortas. However, in ethanol-treated aortas, E max was reduced to control level. Moreover, phenylephrine-stimulated release of thromboxane B 2 , a stable metabolite of TXA 2 , was higher in tissues from ethanol-treated rats. Simultaneous measurement of the changes in [Ca 2+ ] i and contraction induced by phenylephrine showed that both parameters are higher in the rat aorta from ethanol-treated rats. CaCl 2 -induced contraction in free Ca 2+ solution containing phenylephrine was increased in ethanol-treated aortas. Additionally, the enhancement in CaCl 2 -induced contraction was prevented by SQ29548. The major contribution of the present study is that it demonstrates a detailed description of the mechanisms involved in the enhancement of phenylephrine-induced contraction in rat aorta from ethanol-treated rats. We provided evidence that this response was not different among the three periods of treatment employed in this study and that it is maintained by two mechanisms: an increased release of vascular smooth muscle-derived vasoconstrictor prostanoids (probably TXA 2 ) and an enhanced extracellular Ca 2+ influx.