endothelin-1 and Alcoholism

Recent evidence shows that chronic ethanol consumption increases endothelin (ET)-1 induced sustained contraction of trabecular smooth muscle cells of the corpora cavernosa in corpus cavernosum of rats by a mechanism that involves increased expression of ETA and ETB receptors. Our goal was to evaluate the effects of alcohol and diabetes and their relationship to miRNA-155, miRNA-199 and endothelin receptors in the corpus cavernosum and blood of rats submitted to the experimental model of diabetes mellitus and chronic alcoholism. Forty-eight male Wistar rats were divided into four groups: control (C), alcoholic (A), diabetic (D), and alcoholic-diabetic (AD). Samples of the corpus cavernosum were prepared to study the protein expression of endothelin receptors by immunohistochemistry and expression of miRNAs-155 and -199 in serum and the cavernous tissue. Immunostaining for endothelin receptors was markedly higher in the A, D, and AD groups than in the C group. Moreover, a significant hypoexpression of the miRNA-199 in the corpus cavernosum tissue from the AD group was observed, compared to the C group. When analyzing the microRNA profile in blood, a significant hypoexpression of miRNA-155 in the AD group was observed compared to the C group. The miRNA-199 analysis demonstrated significant hypoexpression in D and AD groups compared to the C group. Our findings in corpus cavernosum showed downregulated miRNA-155 and miRNA-199 levels associated with upregulated protein expression and unaltered mRNA expression of ET receptors suggesting decreased ET receptor turnover, which can contribute to erectile dysfunction in diabetic rats exposed to high alcohol levels.

Topics: Alcoholism; Animals; Diabetes Mellitus, Experimental; Endothelin-1; Immunohistochemistry; Male; MicroRNAs; Penis; Rats; Rats, Wistar; Receptor, Endothelin A; Receptor, Endothelin B

Endothelin-1 (ET-1) and nitric oxide are emerging key mediators in the maintenance of mucosal homeostasis, but little is known about these substances in soft oral tissue with alcohol abuse. Hence, we examined the expression of ET-1 and activity of the constitutive nitric oxide synthase (NOS) in buccal mucosa of rats subjected to chronic ethanol diet. The immunometric assays revealed the buccal mucosal level of ET-1 in the controls at 40.2 pg/mg protein and showed a 4.1-fold increase with alcohol diet to 166.2 pg/mg protein. The NOS assays established that comparing to the controls, the alcohol diet group exhibited a 57% decrease in buccal mucosal NOS activity. Moreover, the expression of ET-1 showed an inverse correlation (r = -0.75) with the extent of the induced changes in NOS. The results suggest that an increase in vasoconstrictive ET-1 levels combined with a loss of compensatory action by the constitutive NOS may be responsible for the weakening of oral mucosal defenses in alcoholics.

Topics: Alcoholism; Animals; Cheek; Endothelin-1; Ethanol; Mouth Mucosa; Nitric Oxide Synthase; Nitric Oxide Synthase Type III; Rats; Rats, Sprague-Dawley