Analysis of erectile responses to H 2 S donors in the anesthetized rat

Hydrogen sulfide (H 2 S) is a biologically active endogenous gasotransmitter formed in penile tissue that has been shown to relax isolated cavernosal smooth muscle. In the present study, erectile responses to the H 2 S donors sodium sulfide (Na 2 S) and sodium hydrosulfide (NaHS) were investigated in the anesthetized rat. Intracavernosal injections of Na 2 S in doses of 0.03–1 mg/kg increased intracavernosal pressure and transiently decreased mean arterial pressure in a dose-dependent manner. Blood pressure responses to Na 2 S were rapid in onset and short in duration. Responses to Na 2 S and NaHS were similar at doses up to 0.3 mg/kg, after which a plateau in the erectile response to NaHS was reached. Increases in intracavernosal pressure in response to Na 2 S were attenuated by tetraethylammonium (K + channel inhibitor) and iberiotoxin (large-conductance Ca 2+ -activated K + channel inhibitor), whereas glybenclamide [ATP-sensitive K + (K ATP ) channel inhibitor] and inhibitors of nitric oxide (NO) synthase, cyclooxygenase, and cytochrome P-450 epoxygenase had no effect. These data indicate that erectile responses to Na 2 S are mediated by a tetraethylammonium- and iberiotoxin-sensitive mechanism and that K ATP channels, NO, or arachidonic acid metabolites are not involved. Na 2 S did not alter erectile responses to sodium nitroprusside (NO donor) or cavernosal nerve stimulation, indicating that neither NO nor cGMP metabolism are altered. Thus, Na 2 S has erectile activity mediated by large-conductance Ca 2+ -activated K + channels. It is suggested that strategies that increase H 2 S formation in penile tissue may be useful in the treatment of erectile dysfunction when NO bioavailability, K ATP channel function, or poor responses to PGE 1 are present.