title: Hydrogen sulfide compensates nitric oxide deficiency in murine corpus cavernosum.
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 (H2S) in erection has recently been recognized and is receiving attention as a pharmacological target. Several studies have focused on the effect of H2S on NO-dependent relaxation, but the role of NO on H2S in penile tissue has not been studied yet. Unlike NO, H2S is mainly synthesized from smooth muscle cells rather than endothelial cells. We hypothesized that H2S 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 H2S formation and vasorelaxation induced by l-cysteine, which is the substrate of the H2S 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 H2S 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 in l-cysteine-induced relaxation, and this effect was reversed by AOAA. On the contrary, no change in relaxation to NaHS (exogenous H2S donor) in MCC was observed. L-NNA increased H2S formation stimulated by l-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 H2S plays a compensatory role in the absence of NO by enhancing the relaxation induced by endogenous H2S through CSE and 3-MPST in MCC, without altering downstream mechanisms. We suggest that H2S-targeting drugs may provide the maintenance of compensatory treatment in ED patients. This may be more relevant in ED with severe endothelial dysfunction, as H2S is mainly derived from smooth muscle.
authors: Ege University, Faculty of Pharmacy, Department of Pharmacology, 35100 Bornova-Izmir, Turkey. Electronic address: gunayyetik@gmail.com.
authors: Günay
authors: G
authors: Yetik-Anacak
authors: Ege University, Faculty of Pharmacy, Department of Pharmacology, 35100 Bornova-Izmir, Turkey.
authors: Aycan
authors: A
authors: Dikmen
authors: Department of Pharmacy, University of Naples, Federico II, Via D. Montesano, 49, 80131, Naples, Italy.
authors: Ciro
authors: C
authors: Coletta
authors: Department of Pharmacy, University of Naples, Federico II, Via D. Montesano, 49, 80131, Naples, Italy.
authors: Emma
authors: E
authors: Mitidieri
authors: Ege University, Faculty of Pharmacy, Department of Pharmacology, 35100 Bornova-Izmir, Turkey.
authors: Mehmet
authors: M
authors: Dereli
authors: Department of Pharmacy, University of Naples, Federico II, Via D. Montesano, 49, 80131, Naples, Italy.
authors: Erminia
authors: E
authors: Donnarumma
authors: Department of Pharmacy, University of Naples, Federico II, Via D. Montesano, 49, 80131, Naples, Italy.
authors: Roberta
authors: R
authors: d'Emmanuele di Villa Bianca
authors: Department of Pharmacy, University of Naples, Federico II, Via D. Montesano, 49, 80131, Naples, Italy.
authors: Raffaella
authors: R
authors: Sorrentino
mesh_terms: D000818:Animals; D003545:Cysteine / Q000378:metabolism; D042783:Endothelial Cells / Q000378:metabolism / Q000502:physiology; D007172:Erectile Dysfunction / Q000378:metabolism / Q000503:physiopathology; D006862:Hydrogen Sulfide / Q000378:metabolism*; D008297:Male; D051379:Mice; D032389:Myocytes, Smooth Muscle / Q000378:metabolism / Q000502:physiology; D009569:Nitric Oxide / Q000378:metabolism*; D010410:Penile Erection / Q000502:physiology; D010413:Penis / Q000378:metabolism*; D014664:Vasodilation / Q000502:physiology
chemical_list: D009569:Nitric Oxide; D003545:Cysteine; D006862:Hydrogen Sulfide
keywords: Corpus cavernosum; Erectile function; Hydrogen sulfide; L-NNA; Nω-Nitro-l-arginine; acetylcholine; eNOS; l-cysteine; sodium hydrogen sulfide