Effect of Sildenafil and Rolipram on Adrenergic Responses in Isolated Human and Monkey Corpus Cavernosum

Abstract

ObjectiveEvaluate and compare effects of phosphodiesterase inhibitors (PDEIs), sildenafil and rolipram, on adrenergic contractile responses of human and monkey cavernosal smooth muscle. MethodsHuman penises were obtained from patients undergoing gender reassignment surgery. Isolated human and monkey corpus cavernosum (CC) strips were suspended in tissue bath chambers for isometric tension experiments. The effects of the drugs on precontracted monkey and human CC and neurogenic contractions in human CC were investigated. ResultsBoth sildenafil and rolipram induced concentration-dependent relaxations of human and monkey CC strips precontracted with noradrenaline (NA). The IC50 values, determined by reverse regression for nitroglycerin (NTG), isoprenaline, and sildenafil in monkey CC, were, respectively, 1.5±0.9×10−7M, 3.7±0.6×10−6M, and 1.7±0.7×10−5M. Similarly, in human CC muscle, sildenafil was weaker than NTG as a muscle relaxant. Sildenafil, 1.5μM, reduced neurogenic contractions in human CC due to stimulation of predominantly adrenergic nerves. The suppressant effect of sildenafil on adrenergic transmission was attenuated in CC strips pretreated with Nω-nitro-l-arginine and overcome with a higher stimulus frequency or tetraethylammonium. Rolipram partially inhibited adrenergic excitatory response but without significantly affecting NA-induced contraction. ConclusionsSildenafil and rolipram induced concentration-dependent reversal of human and monkey CC tone mediated by NA. Both PDEIs attenuated contractile adrenergic response of human CC to electrical stimulation. The results also underline the importance of the cyclic adenosine monophosphate-dependent signalling pathway in regulating the tone. PDE4 inhibition in CC is an additional mechanism for erection and potential therapeutic adjunct.