Hydrogen sulfide promotes nitric oxide production in corpus cavernosum by enhancing expression of endothelial nitric oxide synthase.

Recently, hydrogen sulfide (H2S) has been identified as a potential therapy for ED. However, a thorough understanding of its molecular mechanisms of action would be essential to develop H2S as a new therapy for ED. In this study, the effect of H2S on nitric oxide (NO) production, especially through the expression of constitutive nitric oxide synthase (NOS) isoforms-endothelial NOS (eNOS) and neuronal NOS (nNOS) in rat corpus cavernosum (CC) were explored. Real-time PCR studies subsequent to in vitro treatment of sodium hydrosulfide hydrate (NaHS), a stable H2S donor, showed increases in eNOS but not nNOS mRNA. Western blot studies confirmed that the exogenously applied NaHS increased eNOS but not nNOS protein expression in the rat CC. Furthermore, NaHS did not alter the expressed amounts of Caveolin-1 (CAV-1), a dominant inhibitory interaction partner of eNOS, in these tissues. Not surprisingly, NaHS also enhanced the NO production in eNOS-associated membrane fraction of rat CC. Taken together, we ascertain that H2S could exert its proerectile effects by augmenting NO pathway. It appears that H2S would be particularly useful in improving the clinical outcome of ED patients, whose erectile impairment is due to an inherent attenuation of the endothelial NO formation in the cavernosum.