Pharmacological Prevention and Reversion of Erectile Dysfunction After Radical Prostatectomy, by Modulation of Nitric Oxide/cGMP Pathways
Author(s)Gonzalez-Cadavid, Nestor F.
Contributor(s)CHARLES DREW UNIV LOS ANGELES CA
KeywordsAnatomy and Physiology
Medicine and Medical Research
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AbstractDuring Year 2 an experimental article previously submitted was completed and extensively revised for its ulterior recent publication (P-1), describing 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 a large fraction of male patients undergoing this operation and their partners. Therefore, studying the mechanism that triggers it and trying to develop a pharmacological therapy aiming to cure this type of erectile dysfunction, have considerable public health significance. In addition, the completion of Aim 1 was considerably advanced by conducting treatments related to Experiment 3, to demonstrate the effects of a long-term administration of a dose of a PDE5 inhibitor (in this case sildenafil) at one half the dose previously reported by us (P-2) from the results of Experiment 2 during Year 1, as a preventive approach for CVOD and corporal fibrosis. A similar approach was based on the use of a nitric oxide donor, molsidomine, related to Experiment 2. Rat models related to BCNR were applied to establish the similarities and differences between acute (BCNR) and chronic (diabetes) damage to the penile corpora cavernosa, with the common goal of preventing CVOD and the underlying histopathology. All the pending animal treatments in the BCNR model that include lower doses and a different form of oral administration are ongoing, as well as a treatment for reversing the CVOD once established, for experiments 2 and 3. This will continue and be finalized during Year 3. The Year 2 results led to the publication of two additional papers as invited reviews (P5-P6), making a total of six related publications and eight communications to scientific meetings since this grant started.
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