Initial characterization of hydrogen sulfide effects in female sexual function.
BACKGROUND
In our male animal models, hydrogen sulfide (H(2)S) displayed significant vasodilatory and smooth muscle relaxant effects suggestive of an endogenous physiological role in erectile process.


OBJECTIVE
In this first exploratory study, we aimed to identify the existence and mechanism of H(2)S pathway in female sexual physiology.


METHODS
Vaginal and clitoral cavernosal smooth muscle strips from New Zealand white rabbits (N = 12) were exposed to stable H(2)S donor, sodium hydrosulfide hydrate (NaHS.xH(2)O, 100 microM-1.6 mM), in isometric tension studies. The NaHS responses were repeated after incubations with (i) N(omega)-nitro-L-arginine (50 microM), 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) (10 microM) or cis-N-[2-phenylcyclopentyl]-azacyclotridec-1-en-2-amine (MDL 12,330A) (10 microM); and (ii) potassium chloride medium (high K(+) 60 mM/low K(+) 10 mM), tetraethylammonium (10 mM) or glibenclamide (100 microM). Relaxant effect of NaHS was also compared with those of nitroglycerine (0.18-78.2 microM) and sildenafil (0.084-25.3 microM). Additionally, samples (N = 16) were collected for estimations of plasma and tissue H(2)S and expression levels of cystathionine gamma-lyase (CSE) and cystathionine beta-synthase (CBS) proteins.


METHODS
In vitro evidences for H(2)S formation and its physiopharmacological effects.


RESULTS
NaHS produced significant concentration-dependent relaxation of vaginal and cavernosal smooth muscles with inhibitions by combination of ODQ and MDL 12,330A (26.4%), N(omega)-nitro-L-arginine (22.2%), high K(+) (15.1%) or glibenclamide (10.1%). Based on molar potency, NaHS was 18.3 and 6.3 times weaker than nitroglycerine and sildenafil, respectively. Quantitative assays indicated that plasma H(2)S level was 16.5 +/- 2.58 microM, and H(2)S was synthesized in the clitoral and vaginal smooth muscles (1.8 and 3.9 nmol/mg soluble protein compared with 26.5 nmol/mg in the liver: positive control). Similarly, western blotting identified the protein expression bands of CSE (44.5 kDa) and CBS (63 kDa) in these genital tissue samples.


CONCLUSIONS
These pilot studies clearly indicate the smooth muscle relaxant effect of H(2)S in female genital tract, mediating through cyclic adenosine 3':5'-monophosphate, nitric oxide-cyclic guanosine monophosphate and K(+)(ATP) channels. Taken together with biochemical and molecular evidences for endogenous formation, H(2)S pathway could be a contributing factor in female sexual responses.
Srilatha
Balasubramanian
B
Department of Obstetrics and Gynecology, Yong Loo Lin School of Medicine, National University Health System, Singapore. obgsb@nus.edu.sg
Hu
Lingxu
L
Adaikan
Ganesan P
GP
Moore
Philip K
PK
D000818:Animals; D002987:Clitoris / Q000187:drug effects*; D005260:Female; D006862:Hydrogen Sulfide / Q000097:blood / Q000494:pharmacology*; D066298:In Vitro Techniques; D023421:Models, Animal; D009130:Muscle, Smooth / Q000187:drug effects*; D010865:Pilot Projects; D011817:Rabbits; D013223:Statistics as Topic; D013997:Time Factors; D014621:Vagina / Q000187:drug effects*
D006862:Hydrogen Sulfide