Chronic ethanol consumption enhances phenylephrine-induced contraction in the isolated rat aorta

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 Emax from phenylephrine were observed among the groups. SQ29548 ([1S-[1 alpha-2 alpha(Z)3 alpha, 4 alpha]]-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, Emax 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 [Ca2+](i) and contraction induced by phenylephrine showed that both parameters are higher in the rat aorta from ethanol-treated rats. CaCl2-induced contraction in free Ca2+ solution containing phenylephrine was increased in ethanol-treated aortas. Additionally, the enhancement in CaCl2-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 Ca2+ influx.