Ethanol consumption increases endothelin-1 expression and reactivity in the rat cavernosal smooth muscle

摘要

Aims: We investigated the effects of chronic ethanol consumption on the cavernosal smooth muscle (CSM) reactivity to endothelin-1 (ET-1) and the expression of ET system components in this tissue. Methods: Male Wistar rats were treated with heavy dose of ethanol (20% v/v) for 6 weeks. Reactivity experiments were performed in the isolated rat CSM. Plasma and CSM nitrate generation and also superoxide anion generation in rat CSM were measured by chemiluminescence. Protein and mRNA levels of prepro- ET-1, endothelin-converting enzyme-1 (ECE-1), ETA and ETB receptors,eNOS, nNOS and iNOS were assessed by western immunoblotting and quantitative real-time polymerase chain reaction, respectively. Results: Chronic ethanol consumptionincreased plasma ET-1 levels and the contractile response induced by this peptide in the isolated CSM. The relaxation induced by acetylcholine, but not IRL1620, a selective ETB receptor agonist, was reduced in CSMfrom ethanol-treated rats. BQ123, a selective ETA receptor antagonist, produced a rightward displacement of the ET-1 concentration-response curves in CSMfrom control, but not ethanol-treated rats. Reduced levels of nitrate were found in the plasma and CSM from ethanol-treated rats. Ethanol consumption increased superoxide anion generation in the rat CSM. The mRNA levels of pre-pro-ET-1, ECE-1, ETA and ETB receptors, eNOS, nNOS and iNOS were not altered byethanol consumption. Protein levels of ET-1, ETA receptor and iNOS werehigher in the CSM from rats chronically treated with ethanol. Conclusion: The major findings of the present study are that heavy ethanol consumption increases plasma ET-1 levels and the contraction induced by the peptide in the CSM. Increased CSMreactivity to ET-1 and altered protein levels of ET-1 and ETA receptorscould play a role in the pathogenesis of erectile dysfunction associated with chronic ethanol consumption.