Neuronal Nitric Oxide Signaling Regulates Erection Recovery After Cavernous Nerve Injury

Abstract

Nitric oxide is the major neuronal mediator of penile erection but its role in erectile function status after cavernous nerve injury is uncertain. We determined the function of neuronal nitric oxide signaling in the pathobiology of erectile function recovery after partial cavernous nerve injury using genetic and pharmacological mouse experimental paradigms. Erectile function was evaluated in 5 to 7 wild-type and neuronal nitric oxide synthase-α knockout mice per group 1, 3 and 7 days after unilateral crush or sham injury, at day 7 in wild-type mice treated with the nitric oxide synthase inhibitor L-NAME (l-nitro arginine methyl ester) (Sigma-Aldrich®) at baseline and for 6 days after unilateral crush injury. Apoptosis in the penis was evaluated by Western blot analysis of p-Akt-S473, 3-nitrotyrosine and caspase-3 after bilateral crush injury. Intracavernous pressure was significantly decreased at 1, 3 and 7 days in wild-type mice but only at day 1 in knockout mice after unilateral crush injury compared with sham treatment values (p <0.05). L-NAME treated wild-type mice had improved erectile function compared with the vehicle treated group at day 7 after unilateral crush injury (p <0.05). In penes p-Akt-S473 was significantly decreased in vehicle treated (p <0.05) but not in L-NAME treated wild-type mice. In penes 3-nitrotyrosine was significantly decreased in L-NAME treated wild-type and vehicle treated knockout mice (p <0.05). Caspase-3 in penes was significantly increased in vehicle treated (p <0.05) but not in L-NAME treated wild-type mice and vehicle treated knockout mice. Neuronal nitric oxide signaling regulates erectile function recovery early after partial cavernous nerve injury, exerting an inhibitory role via the induction of apoptotic change in penile tissue. Therapeutic strategies to improve erectile function recovery after radical prostatectomy may consider targeting pathogenic sites of nitric oxide neurobiology.