Characterization of relaxant mechanism of H2S in mouse corpus cavernosum

The aim of this study was to investigate the mechanism of H2S-induced relaxation in mouse corpus cavernosal tissue. l-cysteine (10(-6)x10(-3)mol/L) and exogenous H2S (NaHS; 10(-6) to 10(-3)mol/L) induced concentration-dependent relaxation. l-cysteine-induced relaxations was reduced by d,l-propargylglycine, a cystathionine gamma lyase (CSE) inhibitor but not influenced by aminooxyacetic acid, a cystathionine beta synthase (CBS) inhibitor. l-cysteine induced relaxations, but not of those of H2S diminished in endothelium-denuded tissues. N-nitro-l-arginine (l-NA; 10(-4)mol/L), a nitric oxide synthase inhibitor, and ODQ (10(-4)mol/L), a guanylyl cyclase inhibitor, increased the H2S-induced relaxation. Zaprinast (5x10(-6)mol/L) and sildenafil (10(-6)mol/L), phosphodiesterase inhibitors, inhibited H2S-induced relaxation. Adenylyl cyclase inhibitors N-ethylmaleimide (2.5x10(-5)mol/L) and SQ22536 (10(-4)mol/L) reduced relaxation to H2S. Also, H2S-induced relaxation was reduced by KCl (50mmol/L), 4-aminopyridine (10(-3)mol/L), a K-v inhibitor, glibenclamide (10(-5)mol/L), a K-ATP inhibitor or barium chloride (10(-5)mol/L), a K-IR inhibitor. However, H2S-induced relaxation was not influenced by apamin (10(-6)mol/L), a SKCa2+ inhibitor, charybdotoxin (10(-7)mol/L), an IKCa2+ and BKCa2+ inhibitor or combination of apamin and charybdotoxin. Nifedipine (10(-6)mol/L), an L-type calcium channel blocker and atropine (10(-6)mol/L), a muscarinic receptor blocker, inhibited H2S-induced relaxation. However, H2S-induced relaxation was not influenced by ouabain (10(-4)mol/L), a Na+/K+-ATPase inhibitor. This study suggests that H2S endogenously synthesizes from l-cysteine by CSE endothelium-dependent in mouse corpus cavernosum tissue, and exogenous H2S may cause endothelium-independent relaxations via activation of K channels (K-ATP channel, K-V channels, K-IR channels), L-type voltage-gated Ca2+ channels, adenylyl cyclase/cAMP pathway and muscarinic receptor, and there is the interaction between H2S and NO/cGMP.