Pharmacological Prevention and Reversion of Erectile Dysfunction After Radical Prostatectomy, by Modulation of Nitric Oxide/cGMP Pathways
Abstract
During years 1 and 2 we have shown that long-term sustained administration of high doses of PDE5 inhibitors (tadalafil and sildenafil, previously vardenafil), prevented in a rat model of cavernosal nerve damage post-radical prostatectomy the erectile dysfunction (corporal veno-occlusive dysfunction or CVOD) and the underlying penile corporal histopathology resulting from this surgery for prostate cancer in men. Now, we have shown that much lower doses of sildenafil, combined or not with a nitric oxide donor, molsidomine, also correct the CVOD, although so far the stimulation of smooth muscle repair and decrease of fibrosis in the corpora cavernosa do not seem to occur (ongoing assays). We have also studied in this model the effect of implanting muscle derived stem cells (MDSC) into the corpora in the presence or absence of low dose sildenafil (ongoing). During the no-cost extension we aim to complete these studies and determine whether sildenafil stimulates nerve terminal regeneration in the corpora, and, if possible, examine a complementary hypothesis to explain the correction of CVOD by low doses of sildenafil based on secondary tissue targets. Our results pioneered and provide a scientific justification for the emerging shift from the current "on demand/sporadic" therapy of post-radical prostatectomy patients with PDE5 inhibitors, towards their long-term daily administration in the novel "penile preservation post-radical prostatectomy" clinical approach.
Document Details
- Document Type
- Technical Report
- Publication Date
- Mar 01, 2010
- Accession Number
- ADA547286
Entities
People
- Nestor F. Gonzalez-cadavid