L-arginine and tetrahydrobiopterin, but not sodium nitrite partially restored erectile dysfunction in aged rats.

Aging is associated with erectile dysfunction (ED), in which nitric oxide synthase (NOS) activity and NO bioavailability are reduced due to deficiencies of NOS cofactor (tetrahydrobiopterin, BH(4)) and substrate (L-arginine). We determined whether the prolonged treatment with sodium nitrite (NaNO(2)) as a storage form of NO ameliorates ED in aged rats. Male Sprague-Dawley rats were divided: younger, aged and NaNO(2)-treated (20 mg/kg per day) aged groups. The erectile (intracavernosal pressure [ICP]/mean arterial pressure [MAP]) and corpus cavernous (CC) responses were evaluated after 12 weeks. The ICP/MAP in aged rats was lower than in young controls, which was not improved by the NaNO(2) treatment. Immunohistochemical (IHC) staining for endothelial NOS and collagen deposition was performed. We assayed NO indirectly by measuring the level of its stable end products, nitrite/nitrate, using the Griess reagent. The relaxations to ACh and EFS in the aged group were considerably less than in the younger group, which were normalized by acute incubations of l-arginine or BH(4) of aged CC. In conclusion, NaNO(2) treatment did not restore erectile response while nitrate levels were enhanced in aged penis. The cofactor or substrate administrations, but not chronic exogenous modulation of NO system may be beneficial in aged men with ED.

The effect of intracavernosal avanafil, a newer phosphodiesterase-5 inhibitor, on neonatal type 2 diabetic rats with erectile dysfunction.

OBJECTIVE: To determine the effect of avanafil, a novel phosphodiesterase-5 inhibitor, on the treatment of erectile dysfunction associated with type 2 diabetes mellitus (T2DM). METHODS: 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. RESULTS: 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. CONCLUSION: 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.