SMOOTH-MUSCLE TONE REGULATION IN RABBIT CAVERNOSAL AND SPONGIOSAL TISSUE BY CYCLIC-AMP-DEPENDENT AND CYCLIC-GMP-DEPENDENT MECHANISMS

The relaxing effects of several specific and nonspecific inhibitors of phosphodiesterases (PDE) on rabbit isolated corpus cavernosum (CC) an d spongiosum (CS) were investigated. Preparations were mounted in orga n baths, and isometric tension was recorded. The results were compared with the effects of direct administration of analogs of the second me ssenger cyclic nucleotides and the effects of forskolin, a direct stim ulator of adenylate cyclase, and the nitric oxide donor 3-morpholinosy dnonimine (SIN 1). All drugs relaxed the phenylephrine-induced contrac tions in CC and CS in a dose-dependent fashion. In CC: and CS, type II I (SK&F 95654) and type V (zaprinast and dipyramidole) PDE inhibitors, as well as the nonspecific inhibitors papaverine and trequinsin, show ed no differences in IC50. The type IV inhibitor rolipram relaxed CC a nd CS at significantly lower concentrations (p<0.005) than any other P DE 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 cycla se and effectively inhibits contractions in CC and CS. Activation of a denylate cyclase by forskolin also was highly effective (p<0.005). It is concluded that PDE inhibition constitutes an effective relaxing mec hanism in rabbit CC and CS. The marked effects of the different types of PDE inhibitors support the importance of cyclic guanosine 3',5'-mon ophosphate and cyclic adenosine 3',5'-monophosphate in smooth muscle r elaxation in erectile tissue.