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

Purpose: Zaprinast, dipyridamole and sildenafil were injected into the corp ora cavernosa of cats to determine whether changes in the steady state leve l of cyclic guanosine monophosphate (cGMP) induced by inhibiting type 5 pho sphodiesterase would cause an erectile response. Materials and Methods: Increases in intracavernous pressure, penile length and erectile response duration were determined after intracavernous injecti on of the type 5 cGMP specific phosphodiesterase inhibitors zaprinast, dipy ridamole 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 phosphodie sterase inhibitors were compared to a control triple drug combination of 1. 65 mg. papaverine, 0.5 mug. PGE1 and 25 mug. phentolamine. Results: Each selective type 5 phosphodiesterase inhibitor caused dose rela ted increases in intracorporeal pressure and penile length. However, none o f the compounds was as effective as the control drug combination of papaver ine, phentolamine and PGE1. Combining zaprinast with sodium nitroprusside l ed to further increases in pressure and erectile response duration that mor e closely resembled the control drug response. Combining zaprinast with PGE 1 led to a response that was indistinguishable from the control response. Conclusions: The results of these feline studies establish that, administer ing 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 combin ing a selective type 5 phosphodiesterase inhibitor with PGE1 may be highly effective local therapy for erectile dysfunction and an acceptable alternat ive to other current forms of treatment.