Role of endogenous hydrogen sulfide in neurogenic relaxation of rat corpus cavernosum.
Relaxation of corpus cavernosum during penile erection is mediated by a non-adrenergic non-cholinergic (NANC) neurotransmission and by the endothelium via the release of nitric oxide. Hydrogen sulfide (H(2)S) is an endogenous gaseous mediator which is a potent vasodilator and a neurotransmitter. This study was initiated to characterize the role of H(2)S in NANC neurogenic transmission in rat corpus cavernosum. The expression of H(2)S producing enzymes was assessed using RT-PCR as well as Western blotting and showed the expression of cystathionine γ-lyase (CSE) in rat corporal tissue. Homogenates from rat corpus cavernosum convert l-cysteine to H(2)S and this was partially inhibited by a CSE inhibitor, propargylglycine. Electrical stimulation of corporal tissue strips caused NANC relaxation. This neurogenic relaxation was significantly enhanced by inhibition of CSE by propargylglycine indicating that endogenously produced H(2)S may have a negative regulatory role in neurogenic relaxation of rat corpus cavernosum. To investigate this further we used physiologically relevant concentrations of exogenous NaHS, and showed that nanomolar concentrations could inhibit corporal relaxation induced by a nitroxyl (HNO) donor (Angeli's salt) but not with nitrosonium (NO(+)) or NO donors. This suggests that an interaction between endogenously produced H(2)S and nitroxyl (HNO) might be involved in erectile function.
Department of Medicine, UCL Medical School, University College London, UK.
Mehdi
M
Ghasemi
Ahmad R
AR
Dehpour
Kevin P
KP
Moore
Ali R
AR
Mani
D000480:Alkynes / Q000494:pharmacology; D000818:Animals; D003541:Cystathionine beta-Synthase / Q000235:genetics / Q000378:metabolism; D003542:Cystathionine gamma-Lyase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005998:Glycine / Q000031:analogs & derivatives / Q000494:pharmacology; D006862:Hydrogen Sulfide / Q000378:metabolism* / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009126:Muscle Relaxation / Q000502:physiology*; D009589:Nitrogen Oxides / Q000494:pharmacology; D010410:Penile Erection / Q000502:physiology; D010413:Penis / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000480:Alkynes; D009589:Nitrogen Oxides; C009055:propargylglycine; D003541:Cystathionine beta-Synthase; D003542:Cystathionine gamma-Lyase; C039900:nitroxyl; D005998:Glycine; D006862:Hydrogen Sulfide