The effect of sildenafil on apomorphine-evoked increases in intracavernouspressure 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 Dawl ey rats after administration of apomorphine (100 or 250 mu g./kg. subcutane ously). Sildenafil (100 mu g./kg. intravenously) was then given 10 min. aft er a second dose of apomorphine. The time to first response, duration of re sponse, 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 f irst, tonic response was 58 +/- 3 mm. Hg, and a superimposed, burst like in crease in pressure elevated this further to 81 +/- 6 mm. Hg. Bilateral tran section of the pudendal nerves abolished the burstlike pressure changes; bi lateral transection of the cavernous nerves prevented both responses. The d uration of the apomorphine-induced increase in intracavernous pressure was significantly(p = 0.003) prolonged by sildenafil (100 mu g./kg.) from 37 +/ - 4 to 62 +/- 11 s (n = 6). The overall intracavernous pressure response to apomorphine (100 mu g./kg.), measured as the area under the curve, was sig nificantly (p = 0.003) increased by sildenafil (100 mu g./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 represent s a simple model to evaluate the effect of drugs on erectile function. Usin g this model we have shown that apomorphine elicits a rise in intracavernou s pressure that can be prolonged by sildenafil. These results suggest that there may be a role for the combination of apomorphine and sildenafil in th e management of erectile dysfunction.