Smooth muscle tone regulation in rabbit cavernosal and spongiosal tissue by cyclic AMP- and cyclic GMP-dependent mechanisms.
The relaxing effects of several specific and nonspecific inhibitors of phosphodiesterases (PDE) on rabbit isolated corpus cavernosum (CC) and spongiosum (CS) were investigated. Preparations were mounted in organ baths, and isometric tension was recorded. The results were compared with the effects of direct administration of analogs of the second messenger cyclic nucleotides and the effects of forskolin, a direct stimulator of adenylate cyclase, and the nitric oxide donor 3-morpholinosydnonimine (SIN 1). All drugs relaxed the phenylephrine-induced contractions in CC and CS in a dose-dependent fashion. In CC and CS, type III (SK&F 95654) and type V (zaprinast and dipyramidole) PDE inhibitors, as well as the nonspecific inhibitors papaverine and trequinsin, showed no differences in IC50. The type IV inhibitor rolipram relaxed CC and CS at significantly lower concentrations (p < 0.005) than any other PDE inhibitor, and in CC the type III and IV inhibitor zardaverine was more potent (p < 0.05) than SK&F 95654. SIN 1 stimulates guanylate cyclase and effectively inhibits contractions in CC and CS. Activation of adenylate cyclase by forskolin also was highly effective (p < 0.005). It is concluded that PDE inhibition constitutes an effective relaxing mechanism in rabbit CC and CS. The marked effects of the different types of PDE inhibitors support the importance of cyclic guanosine 3',5'-monophosphate and cyclic adenosine 3',5'-monophosphate in smooth muscle relaxation in erectile tissue.
Urology Section, VA Medical Center, Madison, Wisconsin.
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C
Sparwasser
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Drescher
J A
JA
Will
P O
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Madsen
D000818:Animals; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000502:physiology*; D006152:Cyclic GMP / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D008297:Male; D008981:Molsidomine / Q000031:analogs & derivatives / Q000494:pharmacology; D009129:Muscle Tonus / Q000502:physiology*; D009130:Muscle, Smooth / Q000502:physiology*; D010413:Penis / Q000033:anatomy & histology / Q000502:physiology*; D010656:Phenylephrine / Q000494:pharmacology; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D011817:Rabbits
D010726:Phosphodiesterase Inhibitors; D005576:Colforsin; D010656:Phenylephrine; C002385:linsidomine; D008981:Molsidomine; D000242:Cyclic AMP; D006152:Cyclic GMP