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

Hydrogen sulfide (H...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...S donors sodium sulfide (Na...S) and sodium hydrosulfide (NaHS) were investigated in the anesthetized rat. Intracavernosal injections of Na...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...S were rapid in onset and short in duration. Responses to Na...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...S were attenuated by tetraethylammonium (K+ channel inhibitor) and iberiotoxin (large-conductance Ca...-activated K+ channel inhibitor), whereas glybenclamide [ATP-sensitive K+ (K...) 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 Na2S are mediated by a tetraethylammonium- and iberiotoxin-sensitive mechanism and that K... channels, NO, or arachidonic acid metabolites are not involved. Na...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...S has erectile activity mediated by large-conductance Ca...-activated K+ channels. It is suggested that strategies that increase H...S formation in penile tissue may be useful in the treatment of erectile dysfunction when NO bioavailability, K... channel function, or poor responses to PGE... are present. (ProQuest: ... denotes formulae/symbols omitted.)