Characterization of relaxant mechanism of H 2 S in mouse corpus cavernosum

Summary The aim of this study was to investigate the mechanism of H 2 S‐induced relaxation in mouse corpus cavernosal tissue. l ‐cysteine (10 −6  × 10 −3  mol/L) and exogenous H 2 S (Na HS ; 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 H 2 S diminished in endothelium‐denuded tissues. N ω ‐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 H 2 S‐induced relaxation. Zaprinast (5 × 10 −6  mol/L) and sildenafil (10 −6  mol/L), phosphodiesterase inhibitors, inhibited H 2 S‐induced relaxation. Adenylyl cyclase inhibitors N ‐ethylmaleimide (2.5 × 10 −5  mol/L) and SQ 22536 (10 −4  mol/L) reduced relaxation to H 2 S. Also, H 2 S‐induced relaxation was reduced by KC l (50 mmol/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, H 2 S‐induced relaxation was not influenced by apamin (10 −6  mol/L), a SK C a 2+ inhibitor, charybdotoxin (10 −7  mol/L), an IK C a 2+ and BK C a 2+ 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 H 2 S‐induced relaxation. However, H 2 S‐induced relaxation was not influenced by ouabain (10 −4  mol/L), a Na + /K + ‐ ATP ase inhibitor. This study suggests that H 2 S endogenously synthesizes from l ‐cysteine by CSE endothelium‐dependent in mouse corpus cavernosum tissue, and exogenous H 2 S may cause endothelium‐independent relaxations via activation of K channels ( K ATP channel, K V channels, K IR channels), L‐type voltage‐gated Ca 2+ channels, adenylyl cyclase/ cAMP pathway and muscarinic receptor, and there is the interaction between H 2 S and NO / cGMP .