Search

It has been extensively demonstrated that hydrogen sulfyde (H2S) is implicated is several physiological and pathological conditions (J Mol Med, 2012 Mar;90(3):255-63). In particular, it has been shown that H2S causes relaxation in human penile tissues (Proc Natl Acad Sci USA, 2009 Mar 17;106(11):4513-8) and inhibits phosphodiesterase (PDE) activity in vessels (ATVB 2010, Oct;30(10):1998-2004). Beside sildenafil increases H2S generation in human bladder (Eur Urol. 2012 Dec;62(6):1174-80) and tadalafil in myocardial tissues (Circulation 2009, 120:S31-S36). Therefore, our aim was to demonstrate the link between H2S and PDE-5 in mice corpus cavernosum tissues. Thus, we investigated the effects of sildenafil (10 μM, 0.5h); PDE-5 inhibitor, on H2S production as well as the H2S -induced relaxations in mice penile tissues. Penile tissues from CD1 mouse corpus cavernosum (MCC) were used. Functional studies were performed by myograph in Krebs solution. Western blot analysis was performed in order to evaluate CBS and CSE expression and methylene blue assay for measurement of H2S levels. In order to investigate functional significance of H2S on sildenafil-induced augmentation of endothelial relaxation in MCC the sildenafil effect was evaluated on acetylcholine (ACh; 10-9-10-4M), L-cysteine (10-6-10-3M) and NaHS-induced relaxations in presence or not of CSE enzyme inhibitor PPG (10 μM, 0.5h). In order to achieve this issue the H2S production in MCC tissues was also evaluated by incubating the penile tissue with sildenafil in presence or absence of the CSE inhibitor PPG (10 μM, 0.5h) Both CBS and CSE were expressed in MCC and the enzymes efficiently converted L-cysteine into H2S. Further we showed that sildenafil caused a significant increase in H2S production and this augmentation was reversed by CSE inhibition. We found that sildenafil induced an increase in both ACh and L-cysteine-induced relaxations and these augmentations reversed by CSE inhibitor PPG in MCC pre-contracted with phenylephrine (3.10-5M). Beside sildenafil did not significantly increase the NaHS -induced relaxations. Therefore we suggest that both gaseous transmitters NO and H2S affect sildenafil action. In particular our results demonstrate that sildenafil effect is partially mediated by H2S pathway. Thus, H2S signaling may represent a new mechanism involved in the effect of sildenafil on erectile dysfunction.

Öz bulunamadı.

WOS: 000350546100004, PubMed ID: 24661203, The ability to get and keep an erection is important to men for several reasons and the inability is known as erectile dysfunction (ED). ED has started to be accepted as an early indicator of systemic endothelial dysfunction and subsequently of cardiovascular diseases. The role of NO in endothelial relaxation and erectile function is well accepted. The discovery of NO as a small signalling gasotransmitter led to the investigation of the role of other endogenously derived gases, carbon monoxide (CO) and hydrogen sulphide (H2S) in physiological and pathophysiological conditions. The role of NO and CO in sexual function and dysfunction has been investigated more extensively and, recently, the involvement of H2S in erectile function has also been confirmed. In this review, we focus on the role of these three sister gasotransmitters in the physiology, pharmacology and pathophysiology of sexual function in man, specifically erectile function. We have also reviewed the role of soluble guanylyl cyclase/cGMP pathway as a common target of these gasotransmitters. Several studies have proposed alternative therapies targeting different mechanisms in addition to PDE-5 inhibition for ED treatment, since some patients do not respond to these drugs. This review highlights complementary and possible coordinated roles for these mediators and treatments targeting these gasotransmitters in erectile function/ED. Linked ArticlesThis article is part of a themed section on Pharmacology of the Gasotransmitters. To view the other articles in this section visit, Turkish Academia Young investigator award programmeTurkish Academy of Sciences; TUBA-GebipTurkish Academy of Sciences; Turkish Scientific Research Council TUBITAKTurkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK) [109S453, 109S432]; EBILTEMEge University; Conselho Nacional de Desenvolvimento Cientifico e Tecnologico; CNPqNational Council for Scientific and Technological Development (CNPq); Fundacao de Amparo a Pesquisa e Inovacao do Estado de Santa Catarina; FAPESC; COST actionEuropean Cooperation in Science and Technology (COST) [BM1005], The authors would like to thank the financial supports by Turkish Academia Young investigator award programme; TUBA-Gebip (to G. Y. A.), Turkish Scientific Research Council TUBITAK for the grant #109S453 and # 109S432 (to G. Y. A.), EBILTEM (to G. Y. A.), Conselho Nacional de Desenvolvimento Cientifico e Tecnologico; CNPq (to A. E. L.) and Fundacao de Amparo a Pesquisa e Inovacao do Estado de Santa Catarina; FAPESC (to A. E. L.) and the COST action BM1005 (ENOG: European Network on Gasotransmitters).