Hydrogen sulphide: A novel endogenous gasotransmitter facilitates erectile function

Introduction. In a pilot study, we found that the novel gasotransmitter, hydrogen sulfide (H2S), had a vasodilatory and proerectile action on the cavernosum. In the present work, we explored the ability of the cavernosum to synthesize H2S and its mechanism on the cavernosal pathways. Aim. To evaluate the physiopharmacological responses and mechanism in the erectile function of H2S in rabbit cavernosum. Methods. Rabbit corpus cavernosum (CC) smooth muscle tissue (N = 5) was homogenized and incubated with L-cysteine (10 mM) and pyridoxal 5'-phosphate (2 mM) to detect H2S formation. In isometric tension studies on rabbits (N = 12), the effect of sodium hydrogen sulfide (NaHS; stable H,S donor, 100 mu M-3.2 mM) was evaluated on the relaxant and contractile pathways in the cavernous smooth muscle using standard pharmacological tools. Main Outcome Measures. In vitro evidences for cavernosal H2S formation and proerectile pharmacological effects. Results. H2S was readily synthesized in the rabbit CC (2.1 +/- 0.4 nmol/mg protein). In organ bath studies, NaHS consistently relaxed the rabbit CC in a concentration-dependent manner. MDL 12,330A and 1-H-[1,2,4]oxadiazolo-[4,3 -a]-quinoxalin-1-one inhibited the NaHS relaxation by 22.5% and 14.7%, respectively. All three enzyme inhibitors (aminooxyacetic acid [AOAA], P-cyanoalanine [P-CA], and DL-propargylglycine [PAG] [1 mM]) markedly increased the noradrenergic contractile neurotransmission of CC strips to field stimulation with minimal reversal by cysteine (1 mM) indicating the possible inherent inhibition of the relaxant H2S formation. AOAA, P-CA, or PAG had no significant effect on nitrergic relaxation of noradrenaline-precontracted CC strips. Conclusion. These pioneering studies provide evidence for the endogenous formation of H2S and its proerectile relaxant effect on the cavernosum, with the possibility of involvement of the cyclic adenosine monophosphate pathway.