Hydrogen sulfide compensates nitric oxide deficiency in murine corpus cavernosum. (November 2016)

• Record Type: Journal Article
• Authors: Yetik-Anacak, Günay; Dikmen, Aycan; Coletta, Ciro; Mitidieri, Emma; Dereli, Mehmet; Donnarumma, Erminia; d'Emmanuele di Villa Bianca, Roberta; Sorrentino, Raffaella
• Is Part Of: Pharmacological research. Volume 113(2016:Nov.)Part A
• Page Start: 38
• Page End: 43
• Publication Date: 2016-11
• Subjects: Nω-Nitro-l-arginine -- acetylcholine -- l-cysteine -- sodium hydrogen sulfide; Corpus cavernosum -- eNOS -- Hydrogen sulfide -- Erectile function -- L-NNA; Pharmacology -- Periodicals; Pharmacology -- Periodicals; Research -- Periodicals; Médicaments -- Recherche -- Périodiques; Pharmacologie -- Périodiques; 615.105
• DOI: 10.1016/j.phrs.2016.08.015
• Languages: English
• ISSNs: 1043-6618

Abstract

Graphical abstract: Abstract: Erectile dysfunction (ED) is considered as a marker for cardiovascular diseases. Nitric oxide (NO) deficiency is the major cause of erectile dysfunction (ED). The role of hydrogen sulfide (H2 S) in erection has recently been recognized and is receiving attention as a pharmacological target. Several studies have focused on the effect of H2 S on NO-dependent relaxation, but the role of NO on H2 S in penile tissue has not been studied yet. Unlike NO, H2 S is mainly synthesized from smooth muscle cells rather than endothelial cells. We hypothesized that H2 S may compensate for the decreased NO bioavailability and may be beneficial in severe ED where endothelial dysfunction is present. Thus we studied the effect of NO deficiency on H2 S formation and vasorelaxation induced byl -cysteine, which is the substrate of the H2 S producing enzymes in mice corpus cavernosum (MCC). NO deficiency induced by Nω-Nitro-l -arginine (L-NNA) was confirmed by the inhibition of acetylcholine-induced relaxation.l -cysteine, the substrate for the endogenous H2 S production, caused a concentration-dependent relaxation that was reduced by CBS/CSE inhibitor aminooxyacetic acid (AOAA) in MCC strips. L-NNA caused a significant increase inl -cysteine-induced relaxation, and this effect was reversed by AOAA. On the contrary, no change in relaxation to NaHS (exogenous H2 S donor) in MCC was observed. L-NNA increased H2 S formation stimulated byl -cysteine in wild type MCC but not in CSE −/− mice. In parallel, the expression of both cysthationine γ lyase (CSE) and 3-mercaptopyruvate sulphurtransferase (3-MST) was increased, whereas cysthationine-β synthase (CBS) was decreased in eNOS −/− MCC. We conclude that H2 S plays a compensatory role in the absence of NO by enhancing the relaxation induced by endogenous H2 S through CSE and 3-MPST in MCC, without altering downstream mechanisms. We suggest that H2 S-targeting drugs may provide the maintenance of compensatory treatment in ED patients. This may be more relevant in ED with severe endothelial dysfunction, as H2 S is mainly derived from smooth muscle.