Efficacy of Pioglitazone on Erectile Function Recovery in a Rat Model of Cavernous Nerve Injury

OBJECTIVE To examine the effect of pioglitazone on erectile function in a rat model of postprostatectomy erectile dysfunction. METHODS Twenty adult rats were divided into 4 groups: (a) sham, (b) control-bilateral cavernosal nerve crush injury (BCNI), (c) BCNI + low-dose pioglitazone (PioL), and (d) BCNI + high-dose pioglitazone (PioH). Sham and control rats were administered phosphate-buffered saline, whereas PioL and PioH rats received 0.65 and 6.5 mg/kg of pioglitazone, respectively. All treatments were administered by oral gavage for 14 days. After treatment, animals underwent surgery for endpoint cavernosal response to define hemodynamic parameters of erectile function, reported as the ratio of intracavernosal pressure to mean arterial pressure. Corporal tissue was retrieved for histologic and molecular analysis. RESULTS Animals treated with pioglitazone experienced dose-dependent improvements in the ratio of intracavernosal pressure to mean arterial pressure, with the PioH group achieving results similar to the sham group: sham, 0.774; BCNI, 0.421; PioL, 0.616; PioH, 0.758 (P = .0006). PioH animals demonstrated increased expression of endothelial nitric oxide (eNOS) and neuronal nitric oxide (nNOS), whereas both PioL and PioH animals had increased staining for anti-smooth muscle actin antibody and nonsignificant increases in cyclic guanosine monophosphate (cGMP). CONCLUSION Pioglitazone improves erectile function in rats undergoing BCNI via a nitric oxide-mediated pathway. (C) 2014 Elsevier Inc.