Role of Oxidative Stress in the Pathophysiological Mechanism of Erectile Dysfunction

Abstract

Center for Advanced Research in HumanReproduction, Infertility and Sexual Function, GlickmanUrological Institute, Cleveland Clinic Foundation, Glickman Urological Institute, Marymount Hospital,and the `Department of Internal Medicine and Pediatrics,Case Western Reserve University, MetroHealth MedicalCenter, Cleveland, Ohio.Erectile dysfunction (ED) is defined as the inability toachieve or maintain erections sufficient for satisfactorysexual intercourse (NIH Consensus Conference, 1993).It is estimated that the prevalence of ED will double inthe next 25 years. Normal erectile function depends ona precise balance between psychological, hormonal,neurological, vascular, and cavernosal factors. There-fore, an alteration in any one or combination of thesefactors may lead to ED. For many years, the complexinteraction between the origin of impulse and thenormal erectile response was not clearly understood. Itwas not until the early 1990s when the roles of centraland peripheral phenomena in the normal erectileresponse was proposed. The identification of the rolesof various mediators, as well as their interactions, innormal erectile function is a major development in thestudy of ED.Production of nitric oxide (NO) plays a centralphysiological role in erections. The endothelium is theprimary source of NO (Burnett, 1997). The pathophys-iological mechanism of endothelial dysfunction ismultifactorial, and the major outcome is impairedrelease of NO, which leads to ED. Although NO-mediated relaxation plays a central role in erections,other mediators, such as prostaglandins, endothelin, andbradykinins, are also important in maintaining peniletone. Researchers have made great strides in the pasttwo decades in identifying the pathophysiologicalmechanism in ED. However, the precise pathophysio-logical mechanism is still unclear.There is a growing interest among researchers re-garding the role of oxidative stress in the pathophysi-ological mechanism of ED. Oxidative stress occurs whenthere is an imbalance between pro-oxidants and theability of the antioxidants to scavenge excess reactiveoxygen species. The role of oxidative stress and reactiveoxygen species has been extensively evaluated in thepathophysiological mechanisms of male and femaleinfertility. However, its role in ED has not beeninvestigated comprehensively. Initial reports from bothin vitro and in vivo studies have shown a significantassociation between the production of reactive oxygenspecies and erectile dysfunction, especially in diabeticanimal models.In this article, we discuss the role of oxidative stress inthe pathophysiological mechanism of ED and thetherapeutic interventions and preventive strategies thatmay be beneficial in restoring endothelial function andnormal erectile function.