Sparwasser C, Drescher P, Will J A, Madsen P O
Urology Section, VA Medical Center, Madison, Wisconsin.
J Urol. 1994 Dec;152(6 Pt 1):2159-63. doi: 10.1016/s0022-5347(17)32343-1.
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.
研究了几种磷酸二酯酶（PDE）特异性和非特异性抑制剂对兔离体海绵体（CC）和海绵体肌（CS）的舒张作用。将组织标本置于器官浴槽中，记录等长张力。将结果与直接给予第二信使环核苷酸类似物的作用、腺苷酸环化酶直接刺激剂福斯高林以及一氧化氮供体3-吗啉代辛二酰亚胺（SIN 1）的作用进行比较。所有药物均以剂量依赖性方式舒张苯肾上腺素诱导的CC和CS收缩。在CC和CS中，III型（SK&F 95654）和V型（扎普司特和双嘧达莫）PDE抑制剂以及非特异性抑制剂罂粟碱和曲喹辛在半数抑制浓度（IC50）上无差异。IV型抑制剂咯利普兰在显著低于其他任何PDE抑制剂的浓度下（p < 0.005）舒张CC和CS，在CC中，III型和IV型抑制剂扎达维林比SK&F 95654更有效（p < 0.05）。SIN 1刺激鸟苷酸环化酶并有效抑制CC和CS中的收缩。福斯高林激活腺苷酸环化酶也非常有效（p < 0.005）。结论是，PDE抑制是兔CC和CS中的一种有效舒张机制。不同类型PDE抑制剂的显著作用支持了环鸟苷酸3',5'-单磷酸和环腺苷酸3',5'-单磷酸在勃起组织平滑肌舒张中的重要性。
