Analysis of NOS isoform changes in a post radical prostatectomy model of erectile dysfunction

Abstract

Optimal treatment of erectile dysfunction (ED) following radical prostatectomy remains a subject of much controversy and is a significant concern for prostate cancer patients requiring surgical intervention. Neural stimulation involving nitric oxide synthase (NOS) is a crucial aspect of the normal erection process. In this study NOS isoform interaction was evaluated to improve our understanding of molecular changes pertaining to erection post radical prostatectomy. Bilateral cavernous nerve (CN) resected and control adult male Sprague-Dawley rats were killed 7, 14 and 21 days after injury. RT-PCR, in situ hybridization, Western blot and immunohistochemical analysis were used to evaluate changes in NOS isoform expression and distribution. NOS-I protein was dramatically decreased after CN injury while NOS-III and NOS-II remained unchanged. A profound decrease in smooth muscle and endothelium was observed in the corpora. To our knowledge this is the first report of differential altered NOS isoform protein abundance under conditions which mimic radical prostatectomy. These results show the importance of maintaining at least partial innervation of the penis after surgical intervention and that endothelial and smooth muscle changes resulting from loss of innervation may account for the ED observed in prostatectomy patients.