The Effect of Intracavernosal Avanafil, a Newer Phosphodiesterase-5 Inhibitor, on Neonatal Type 2 Diabetic Rats With Erectile Dysfunction

Abstract

To determine the effect of avanafil, a novel phosphodiesterase-5 inhibitor, on the treatment of erectile dysfunction associated with type 2 diabetes mellitus (T2DM). In 2-day-old rats, T2DM was induced by single intraperitoneal injection of 90 mg/kg of streptozotocin (STZ; i.p.). Erectile responses were evaluated after 10 weeks on intracavernosal injection of avanafil (1 μM) to anesthetized rats and data expressed as intracavernosal pressure (ICP)/mean arterial pressure and total ICP. The relaxant and contractile responses of corpus cavernosum (CC) strips were obtained in vitro studies. ICP/mean arterial pressure and total ICP responses were significantly reduced in T2DM rats compared with controls. Avanafil partially restored diminished ICP responses in diabetic rats. In CC strips from the diabetic group, electrical field stimulation (1-20 Hz)-induced relaxation responses were markedly enhanced by 45%, whereas acetylcholine (ACh; 10(-8)-10(-3))-induced relaxation responses were diminished by 73%. In addition, phenylephrine (PE; 10(-8)-10(-3)) and electrical field stimulation (1-40 Hz)-induced contractile responses were significantly reduced in the diabetic group compared with controls. CC relaxant responses to sodium nitroprusside (SNP, 10(-8)-10(-3)) and avanafil (10(-8)-10(-3)) were unaltered in both groups. The cavernous injection of avanafil in T2DM rats resulted in partial improvement in erectile responses. These findings suggest that intracavernosal administration of avanafil might be beneficial for the treatment of erectile dysfunction in patients with T2DM.