Sildenafil citrate on nitrergic transmission in anococcygeus muscles from the urogenital system of male and female mice.
The effects of sildenafil on nitrergic relaxations were compared in anococcygeus muscles from male and female mice. In muscles from both sexes, sildenafil (10-300 nM) produced a weak, direct relaxation of carbachol-induced tone, and increased both the amplitude and duration of nitrergic relaxations. The most marked effect was on nitrergic duration (300-400% increase with 300 nM sildenafil); no differences in potency were observed between male (EC(50), 30 nM) and female (EC(50), 25 nM). The rate of onset for potentiation of nitrergic duration was similar in both sexes; but, on washout, the effects of sildenafil declined more slowly in the male muscle. Relaxations to both nitric oxide (NO) and sodium nitroprusside were also increased in amplitude and duration by 50 nM sildenafil, while those to forskolin and papaverine were unaffected. The results demonstrate that sildenafil causes a similar, potent and selective potentiation of nitrergic transmission in urogenital smooth muscle from both male and female mice.
Frith
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D
Messengers and Signalling Research Group, School of Biomedical Sciences, King's College London, Hodgkin Building, Guys Campus, SE1 9RT, London, UK.
Gibson
A
A
D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000502:physiology; D009130:Muscle, Smooth / Q000187:drug effects / Q000294:innervation*; D009569:Nitric Oxide / Q000502:physiology*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D010208:Papaverine / Q000494:pharmacology; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D010879:Piperazines / Q000494:pharmacology*; D011687:Purines; D012737:Sex Factors; D000068677:Sildenafil Citrate; D013379:Substrate Specificity; D013450:Sulfones; D009435:Synaptic Transmission / Q000187:drug effects* / Q000502:physiology; D014566:Urogenital System / Q000294:innervation*
D020030:Nitric Oxide Donors; D010726:Phosphodiesterase Inhibitors; D010879:Piperazines; D011687:Purines; D013450:Sulfones; D009599:Nitroprusside; D005576:Colforsin; D009569:Nitric Oxide; D002217:Carbachol; D000068677:Sildenafil Citrate; D010208:Papaverine