In vivo and in vitro investigation of the effects of sildenafil on rat cavernous smooth muscle.

PURPOSE: We investigated the effect of sildenafil on rat erectile tissues in vivo and in vitro. MATERIALS AND METHODS: Intracavernous pressure was recorded in pentobarbital anesthetized, male Sprague-Dawley rats and we studied the effect of 100 or 200 microg/kg(-1) sildenafil given intravenously. In an isolated endothelin-1 contracted strip preparation of rat corpus cavernosum we also assessed the effect of sildenafil on the response to electrical field stimulation of the nerves. RESULTS: Electrical stimulation of the cavernous nerve induced a frequency dependent increase in intracavernous pressure of a mean plus or minus standard error of mean 55 +/- 3 mm Hg at 20 Hz, corresponding to a mean of 47% +/- 2% of mean arterial pressure. The 100 microg/kg(-1) dose did not increase intracavernous pressure but significantly increased mean decay time of the pressure response from 16 +/- 3 to 35 +/- 3 seconds (p <0.001). In vitro sildenafil significantly enhanced the amplitude and duration of the relaxation induced by the electrical stimulation of corpus cavernosum strips in a concentration dependent fashion. CONCLUSIONS: In anesthestized rats sildenafil significantly prolonged the decay period of the intracavernous pressure response induced by electrical stimulation of the cavernous nerve but it did not increase the amplitude. Sildenafil enhanced the amplitude and duration of the relaxant response to electrical field stimulation in isolated corpus cavernosum tissue.

The effect of sildenafil on apomorphine-evoked increases in intracavernous pressure in the awake rat.

PURPOSE: The aim of this study was to develop a quantitative, awake animal model to investigate the effect of sildenafil on centrally-evoked erectile activity. METHODS: Intracavernous pressures were recorded in awake, male Sprague Dawley rats after administration of apomorphine (100 or 250 microg./kg. subcutaneously). Sildenafil (100 microg./kg. intravenously) was then given 10 min. after a second dose of apomorphine. The time to first response, duration of response, and peak intracavernous pressure and area under the response, were measured before and after sildenafil. RESULTS: Apomorphine produced rhythmic increases in intracavernous pressure. The pressure increase consisted of two components. The amplitude of the first, tonic response was 58 +/- 3 mm. Hg, and a superimposed, burst-like increase in pressure elevated this further to 81 +/- 6 mm. Hg. Bilateral transection of the pudendal nerves abolished the burstlike pressure changes; bilateral transection of the cavernous nerves prevented both responses. The duration of the apomorphine-induced increase in intracavernous pressure was significantly (p = 0.003) prolonged by sildenafil (100 microg./kg.) from 37 +/- 4 to 62 +/- 11 s (n = 6). The overall intracavernous pressure response to apomorphine (100 microg./kg.), measured as the area under the curve, was significantly (p = 0.003) increased by sildenafil (100 microg./kg.) from 67 +/- 8 to 142 +/- 31 units (n = 6). N-nitro-L-arginine methyl ester (40 mg./kg. intravenously) prevented the apomorphine-induced responses. CONCLUSIONS: Monitoring intracavernous pressures in the awake rat represents a simple model to evaluate the effect of drugs on erectile function. Using this model we have shown that apomorphine elicits a rise in intracavernous pressure that can be prolonged by sildenafil. These results suggest that there may be a role for the combination of apomorphine and sildenafil in the management of erectile dysfunction.