Animal models of erectile dysfunction (ED): potential utility of non-human primates as a model of atherosclerosis-induced vascular ED

Abstract

Erectile dysfunction (ED) is a prevalent medical condition affecting 18 million men and their sexual partners in the United States alone. In the majority of patients, ED is related to alterations in the flow of blood to or from the penis. Undeniably, significant progress has been made in understanding the multifactorial mechanisms that modulate erectile capacity and predispose one to ED, and this, in turn, has led to the availability of more effective treatment options. Nonetheless, all current therapies have untoward side effects, and moreover, there are still no satisfactory treatments for many patients with ED. Further enhancements in the treatment of ED would logically result from both early intervention and more detailed mechanistic insight into the characteristics of the disease process per se. This fact underscores the importance of improved understanding of the initiation, development and progression of ED. However, to do so requires longitudinal studies on animal models that more closely approximate the corresponding clinical features and time course of human disease. The goal of this report is twofold. First, to provide a brief general overview of the applicability of commonly used animal models for the study of ED. The second and primary goal is to highlight the scientific rationale for using non-human primates to evaluate the impact of atherosclerosis-induced vascular disease on the penile and systemic circulatory systems. This latter goal seems especially relevant in light of the recent literature documenting a link between ED and systemic vascular disease, a finding that has major implications in an aging US male population consuming a high fat diet. Keywords: animal models; atherosclerosis; non-human primates; vascular disease INTRODUCTION Erectile dysfunction (ED) is defined as the inability to achieve or maintain an erection sufficient for satisfactory sexual performance.1 --4 ED often has profound effects on intimate relationships, quality of life and overall self-esteem, causing serious distress and prompting men to seek medical attention. The economic impact of ED is multifaceted, with direct costs that include physician evaluation, pharmacotherapy and diagnostic testing, and indirect costs that include lost time at work, lost productivity and effects on the man's partner, family and coworkers. The Massachusetts Male Aging Study indicates that the prevalence of ED increases sharply with age. ED of some degree of severity is observed in 39% of men aged 40 years and in 67% of men aged 70 years.

Molecular and Histologic Evidence of Novel Erectile Dysfunction Rat Model as an Aging Atherosclerosis Model: A Preliminary Study

“…The key pathophysiology of AS change lies in obstructing arterial inflow by narrowed lumen due to artherosclerotic lesions [1,4,10,17,18]. Hence, without intimal injury, an ED model could not show endothelial dysfunction.…”

“…The key mechanism of endothelial dysfunction lies on NOS. Nitric oxide (NO) is involved in anti-inflammation, anti-platelet aggregation, and anti-oxidative function [8,9,18]. NOS is composed of three isoforms including neuronal NOS (nNOS), eNOS, and inducible NOS.…”

“…Nowadays, these two main components (structural and functional changes) have a tendency to be overlapped [3,18]. Hence, validation of a promising ED model should include these two components together.…”

Nonhuman primate model of persistent erectile and urinary dysfunction following radical prostatectomy: Feasibility of minimally invasive therapy

“…Their main disadvantages are high cost, animal rights sensitivity and specialized husbandry requirements. However, their mating stimuli are more like human beings (site, touch, behavior) than rodents (smell) . Their pre‐coital and post‐coital behavior permits assessments of both mating ability and satisfaction .…”

Association of Hypertension With Erectile Function in Chronic Peripheral Arterial Insufficiency Patients

“…Erectile dysfunction (ED) is a common condition; it affects 18 million men and their sexual partners in the United States and is generally related to changes in blood flow to the penis [1]. Decreased arterial elasticity, high resting heart rate and metabolic syndrome are important cardiovascular risk markers associating arteriosclerosis, a disease associated to, among other things, ED [2].…”