Expression Profiles of eNOS, iNOS, endothelin receptors and microRNAs‐27b, 155 and 199 in the corpus cavernosum of rats submitted to chronic alcoholism and diabetes mellitus.

Abstract

IntroductionEthanol consumption has been described to increase the levels of plasma endothelin‐1 (ET‐1) suggesting that chronic consumption activates endothelinergic pathway and also to affect nitric oxide synthase (NOS) derived nitric oxide (NO) and NOS expression in different tissues. Recent evidence showed that chronic ethanol consumption increases ET‐1‐induced sustained contraction of trabecular smooth muscles cells of the corpora cavernosal in corpus cavernosum of rat by mechanism that involves increased expression of ETA eee and ETB receptors.ObjectivesTo evaluate the effects of chronic ethanol consumption associated with diabetes affected the endothelin system in the cavernosal smooth muscle (CSM) of rats, as well as the effects of chronic ethanol consumption and diabetes on nitric oxide (NO)‐mediated relaxation of cavernosal smooth muscle (CSM).Materials and MethodsCorpus cavernosum were divided into four groups: control, ethanol, diabetic and ethanol‐diabetic of Male Wistar rats. We analyzed protein and gene expression of endothelial NO synthase (eNOS), inducible NO synthase (iNOS) and endothelin receptors (ETA eeeand ETB) by immunohistochemistry and real time‐PCR. The expression of miRNAs‐27a, 199 and 155 by real time‐PCR in corpus cavernosum. It was also evaluated the effect of ethanol consumption associated with diabetes on the relaxation induced by acetylcholine (ACh; 0.01–1000 micromol/L) and in the contraction induced by Endothelin‐1 (ET‐1 0.1 nmol‐ 1μmol L‐1) in organ chambers for measurement of isometric tension.ResultsThe endothelium‐dependent relaxation induced by ACh was decreased in CSM from ethanol, diabetic, ethanol‐diabetic groups when compared with the control group. Immunohistochemistry for eNOS, iNOS, ETA eeeand ETB showed an increase in cavernosal smooth muscle cells in the ethanol, diabetic and ethanol‐diabetic groups when compared with the control group. Similarly, the mRNA levels for eNOs, ETA eeeand ETB were increased in CSM of groups ethanol, diabetic and ethanol‐diabetic and miRNAs‐27a, 155 and 199 were decreased in cavernosal smooth muscle from the ethanol, diabetic and ethanol‐diabetic groups.ConclusionsOur results showed that chronic ethanol consumption associated with diabetes was an impairment of relaxation of CSM from ethanol, diabetic, and ethanol‐diabetic rats that involved a decrease in the NO pathway by endothelium‐dependent mechanisms accompanied by a change in the corpus cavernosum contractile sensitivity. We can also suggest that chronic ethanol consumption associated with diabetes changed the endothelinergic system in the CSM played a role in the pathogenesis of erectile dysfunction, suggesting that these changes of endothelin receptors were regulated by miRNAs‐155, 199.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.