Direct effects of selective type 5 phosphodiesterase inhibitors alone or with other vasodilators on the erectile response in cats.

Abstract

Zaprinast, dipyridamole and sildenafil were injected into the corpora cavernosa of cats to determine whether changes in the steady state level of cyclic guanosine monophosphate (cGMP) induced by inhibiting type 5 phosphodiesterase would cause an erectile response. Increases in intracavernous pressure, penile length and erectile response duration were determined after intracavernous injection of the type 5 cGMP specific phosphodiesterase inhibitors zaprinast, dipyridamole and sildenafil as well as combined zaprinast and prostaglandin E1 (PGE1), and zaprinast and sodium nitroprusside. Systemic arterial pressure was concurrently assessed in these experiments. All responses to phosphodiesterase inhibitors were compared to a control triple drug combination of 1.65 mg papaverine, 0.5 microg PGE1 and 25 microg phentolamine. Each selective type 5 phosphodiesterase inhibitor caused dose related increases in intracorporeal pressure and penile length. However, none of the compounds was as effective as the control drug combination of papaverine, phentolamine and PGE1. Combining zaprinast with sodium nitroprusside led to further increases in pressure and erectile response duration that more closely resembled the control drug response. Combining zaprinast with PGE1 led to a response that was indistinguishable from the control response. The results of these feline studies establish that administering a type 5 phosphodiesterase inhibitor without concomitant administration of a nitric oxide donor or stimulation of the cavernous nerves may have a direct effect on the erectile response. These data also suggest that combining a selective type 5 phosphodiesterase inhibitor with PGE1 may be highly effective local therapy for erectile dysfunction and an acceptable alternative to other current forms of treatment.