Effect of sildenafil and rolipram on adrenergic responses in isolated human and monkey corpus cavernosum.
OBJECTIVE
Evaluate and compare effects of phosphodiesterase inhibitors (PDEIs), sildenafil and rolipram, on adrenergic contractile responses of human and monkey cavernosal smooth muscle.


METHODS
Human 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.


RESULTS
Both sildenafil and rolipram induced concentration-dependent relaxations of human and monkey CC strips precontracted with noradrenaline (NA). The IC(50) values, determined by reverse regression for nitroglycerin (NTG), isoprenaline, and sildenafil in monkey CC, were, respectively, 1.5+/-0.9x10(-7) M, 3.7+/-0.6x10(-6) M, and 1.7+/-0.7x10(-5) M. Similarly, in human CC muscle, sildenafil was weaker than NTG as a muscle relaxant. Sildenafil, 1.5 microM, 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 N omega-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.


CONCLUSIONS
Sildenafil 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.
Lau
Lang-Chu
LC
Department of Obstetrics and Gynaecology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
Adaikan
P Ganesan
PG
D015106:3',5'-Cyclic-GMP Phosphodiesterases / Q000037:antagonists & inhibitors; D000317:Adrenergic alpha-Antagonists; D000818:Animals; D007172:Erectile Dysfunction / Q000188:drug therapy; D006801:Humans; D008252:Macaca fascicularis; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects* / Q000502:physiology; D009126:Muscle Relaxation / Q000187:drug effects* / Q000502:physiology; D009130:Muscle, Smooth / Q000187:drug effects* / Q000502:physiology; D010410:Penile Erection / Q000187:drug effects; D010413:Penis / Q000166:cytology / Q000187:drug effects*; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D010879:Piperazines / Q000494:pharmacology*; D011687:Purines / Q000494:pharmacology; D020889:Rolipram / Q000494:pharmacology*; D000068677:Sildenafil Citrate; D013450:Sulfones / Q000494:pharmacology*
D000317:Adrenergic alpha-Antagonists; D010726:Phosphodiesterase Inhibitors; D010879:Piperazines; D011687:Purines; D013450:Sulfones; D000068677:Sildenafil Citrate; D015106:3',5'-Cyclic-GMP Phosphodiesterases; D020889:Rolipram