Pharmacological Prevention and Reversion of Erectile Dysfunction after Radical Prostatectomy, By Modulation of Nitric Oxide/Cgmp Pathways; Annual rept. 1 Mar 2007-28 Feb 2008

摘要

During Year 1 we aimed to determine the time course of histological and functional changes affecting the penile corpora cavernosa after bilateral cavernosal nerve resection (BCNR) in the rat, as an experimental model for erectile dysfunction subsequent to radical prostatectomy for prostate cancer. This condition seriously affects the quality of life of male patients and their partners. We have now determined that this neuropraxia causes the loss of smooth muscle cells by apoptosis and then an excessive collagen deposition in the penile corpora cavernosa. This in turn is responsible for the impaired corporal compliance leading to corporal veno-occlusive dysfunction (CVOD), seen in these patients, that is in part counteracted by the spontaneous induction of inducible nitric oxide synthase (iNOS) that stimulate nitric oxide and cGMP production. Long-term continuous oral administration of PDE5 inhibitors immediately after BCNR, thus raising cGMP levels, prevents CVOD and the underlying histopathology of the corpora cavernosa. This may soon be translated into the clinic, once the appropriate dosing is established, as a treatment to prevent or counteract erectile dysfunction after radical prostatectomy.