Chronic ethanol consumption enhances phenylephrine-induced contraction in the isolated rat aorta.
J Pharmacol Exp Ther
; 316(1): 233-41, 2006 Jan.
Article
en En
| MEDLINE
| ID: mdl-16174792
ABSTRACT
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.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Aorta Torácica
/
Fenilefrina
/
Cardiotónicos
/
Depresores del Sistema Nervioso Central
/
Etanol
/
Corazón
/
Músculo Liso Vascular
Límite:
Animals
Idioma:
En
Revista:
J Pharmacol Exp Ther
Año:
2006
Tipo del documento:
Article
País de afiliación:
Brasil