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 E(max) from phenylephrine were observed among the groups. SQ29548 ([1S-[1alpha-2alpha(Z)3alpha,4alpha]]-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.
Tirapelli
Carlos R
CR
Universidade de São Paulo, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Avenida do Café s/n, CEP 14040-903, Ribeirão Preto, SP, Brazil.
Al-Khoury
Johny
J
Bkaily
Ghassan
G
D'Orléans-Juste
Pedro
P
Lanchote
Vera L
VL
Uyemura
Sergio A
SA
de Oliveira
Ana M
AM
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects*; D016718:Arachidonic Acid / Q000378:metabolism / Q000502:physiology; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D002316:Cardiotonic Agents / Q000494:pharmacology*; D002492:Central Nervous System Depressants / Q000097:blood / Q000494:pharmacology*; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D019332:Endothelin-1 / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000201:enzymology / Q000502:physiology; D000431:Ethanol / Q000097:blood / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects*; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009569:Nitric Oxide / Q000502:physiology; D010656:Phenylephrine / Q000494:pharmacology*; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013928:Thromboxane A2 / Q000378:metabolism
D001786:Blood Glucose; D002316:Cardiotonic Agents; D002492:Central Nervous System Depressants; D019332:Endothelin-1; D010656:Phenylephrine; D016718:Arachidonic Acid; D009569:Nitric Oxide; D000431:Ethanol; D013928:Thromboxane A2; D011451:Prostaglandin-Endoperoxide Synthases; D002118:Calcium