The investigation of the relaxant mechanism of hydrogen sulfide in isolated corpus cavernosum

In the present study, the relaxant mechanism of hydrogen sulfide was investigated in isolated corpus cavernosum tissue., L-cystein- and sodium hydrogen sulfide- (NaHS; H2S donor; 10-6-10-3) induced relaxant responses on the isolated mouse corpus cavernosum tissue which was pre-contracted by phenylephrine. L-cystein-induced relaxations significantly was reduced by D,L-propargylglycine, cystathionine gama lyase inhibitor whereas not influenced by aminooxyacetic acid, cystathionine beta synthase inhibitor. The relaxant response to NaHS did not change in endotheium-denuded tissues. Nitric oxide synthase inhibitor N?-nitro-L-arginin (10-4 M), guanylyl cyclase inhibitor ODQ (10-4 M) and combination of these inhibitor increased the relaxant response to NaHS. NaHS-induced relaxant response was inhibited by zaprinast (5x10-6 M) and sildenafil (10-6 M), phosphodiesterase inhibitors. NaHS-induced relaxation was significantly reduced by N-Ethylmalemeid (2.5x10-5 M) and SQ22536 (10-4 M), adenylyl cyclase inhibitors. Also, NaHS-induced relaxation was reduced in the presence of high potassium (50 mM), voltage-gated potassium channel inhibitor 4-aminopyridine, ATP-sensitive potassium channel inhibitor glibenclamide (10-5 M), inward rectifier potassium channel inhibitor barium chloride (10-5 M). However, NaHS-induced relaxation was not influenced by small conductance calcium activated potassium channel inhibitor apamin (10-6 M), intermediate and large conductance calcium activated potassium channel inhibitor charybdotoxin (10-7 M) and combination of apamin and charybdotoxin. L-type calcium channel blocker nifedipine and muscarinic receptor blocker atropine inhibited relaxant response to NaHS. However, NaHS-induced relaxation was not influenced by ouabain (10-4 M). We conclude that, in mouse corpus cavernosum tissue H2S may be produced endogenously from L-cysteine by cystathionine gama lyase enzyme; the relaxant effect of H2S endothelium-independent and directly acts on smooth muscle via; i) adenylyl cyclase/cAMP ii) potassium channels iii) L-type calcium channel and iv) muscarinic receptors and, this relaxant effect may be suppressed by NO/sGMP.