Authors: Aversa, Antonio; Caprio, Massimiliano; Rosano, Giuseppe M.C.; Spera, Giovanni

Source: Current Pharmaceutical Design, Volume 14, Number 35, December 2008 , pp. 3768-3778(11)

Publisher: Bentham Science Publishers

Abstract:

Erectile dysfunction (ED) and endothelial dysfunction are common in individuals with multiple cardiovascular risk factors (CRFs) and are longitudinal predictors of cardiovascular events. ED is associated with systemic endothelial cell activation/dysfunction independent from CRFs or from diffuse, unrecognized vascular damage. The pathogenesis of endothelial dysfunction and ED is intimately linked through decreased expression and activation of endothelial nitric oxide (NO) synthase and the subsequent physiologic actions of NO. Furthermore, reduced biologic activity of endotheliumderived NO links atherosclerosis to ED and underscores the role of altered endothelium in the pathogenesis of both conditions. Evidence-based data suggest that daily use of phosphodiesterase type-5 inhibitors (PDE5-i) improves endothelial and erectile functions and that this benefit is lost upon drug withdrawal. Daily PDE5-i may also improve lower tract urinary symptoms related to benign prostatic hyperplasia through a reduction of adrenergic overtone. The relevance for these drugs in the prevention of complications in internal medicine diseases, i.e. cardiovascular disease, clotting disorders and autoimmune disease is uncertain. Finally, endothelial dysfunction is present in testosterone deficiency syndromes and replacement therapy is able to revert ED and to improve endothelial function.

Aim of the present review is to discuss the systemic effects of drugs designed to treat ED, such as testosterone and PDE5- i, with regard to safety, unwanted effects and efficacy in improving endothelial function; finally, a goal-oriented approach to rehabilitation using daily vs. on-demand PDE5-i in difficult patients is discussed.

Keywords: Endothelial dysfunction; nitric oxide; testosterone; phosphodiesterase type-5 inhibitors; benign prostatic hyperplasia; LUTS; rehabilitation; internal medicine

Document Type: Research article

DOI: http://dx.doi.org/10.2174/138161208786898725

Affiliations: 1: Internal Medicine Unit, Medical Pathophysiology Department, “Sapienza” University of Rome, Viale del Policlinico 155, 00161, Rome, Italy.

Publication date: 2008-12-01

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• Current Pharmaceutical Design publishes timely in-depth reviews covering all aspects of current research in rational drug design. Each issue is devoted to a single major therapeutic area. A Guest Editor who is an acknowledged authority in a therapeutic field has solicits for each issue comprehensive and timely reviews from leading researchers in the pharmaceutical industry and academia.
  
  Each thematic issue of Current Pharmaceutical Design covers all subject areas of major importance to modern drug design, including: medicinal chemistry, pharmacology, drug targets and disease mechanism.

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