Sildenafil relaxes rabbit clitoral corpus cavernosum.
The role of phosphodiesterase type 5 inhibition in the modulation of female sexual dysfunction was investigated by assessing its effects on in vitro relaxation of rabbit clitoris. Stimulation of the non-adrenergic, non-cholinergic neurons of the clitorus elicited a frequency-dependent relaxation response. Inhibition of NO synthase with L-NAME (100 microM) or inhibition of soluble guanylate cyclase with ODQ (1.0 microM) almost completely abolished the electrical field stimulation-induced relaxation of clitorus suggesting that NO-cGMP pathway mediates the relaxation response to electrical field stimulation. Similarly, tetrodotoxin, a neuronal sodium channel blocker abolished the electrical field stimulation-induced clitoral relaxation implying a neuronal release of NO contributes to the electrical field stimulation elicited relaxation. Pretreatment of the clitoral corpus cavernosum strips with sildenafil (100 nM) enhanced the electrical field stimulation-induced relaxations both in magnitude and duration. The results suggest that sildenafil enhances electrical field stimulation elicited clitoral relaxation by a NO-cGMP dependent pathway. These data also imply that sildenafil may be useful to treat female sexual dysfunction.
Vemulapalli
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CNS/CV Biological Research, Schering-Plough Research Institute, Kenilworth, NJ 07033, USA. Subbarao.Vemulapalli@SPCorp.com
Kurowski
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S
D015106:3',5'-Cyclic-GMP Phosphodiesterases / Q000037:antagonists & inhibitors*; D000818:Animals; D002987:Clitoris / Q000187:drug effects / Q000294:innervation / Q000502:physiology*; D004558:Electric Stimulation; D005260:Female; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors; D009126:Muscle Relaxation / Q000187:drug effects / Q000502:physiology*; D009130:Muscle, Smooth / Q000187:drug effects* / Q000294:innervation; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D010069:Oxadiazoles / Q000494:pharmacology; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D010879:Piperazines / Q000494:pharmacology*; D011687:Purines; D011810:Quinoxalines / Q000494:pharmacology; D011817:Rabbits; D000068677:Sildenafil Citrate; D013450:Sulfones; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D013779:Tetrodotoxin / Q000494:pharmacology
C095284:1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one; D010069:Oxadiazoles; D010726:Phosphodiesterase Inhibitors; D010879:Piperazines; D011687:Purines; D011810:Quinoxalines; D013450:Sulfones; D009569:Nitric Oxide; D013779:Tetrodotoxin; D000068677:Sildenafil Citrate; D019001:Nitric Oxide Synthase; D015106:3',5'-Cyclic-GMP Phosphodiesterases; D006162:Guanylate Cyclase; D019331:NG-Nitroarginine Methyl Ester