Dietary Modification Is Associated with Normalization of Penile Hemodynamics in Rats Fed a High-Fat Diet

Background: Diet is associated with self-reported indices of sexual health. The mechanisms responsible for these changes remain poorly understood. Aim: To investigate the hemodynamic and histological impact of dietary change in a rat model of hyperlipidemia-associated erectile dysfunction. Methods: 40 2-month old male Sprague-Dawley rats were divided into 4 groups. 10 rats were fed a diet of standard chow and served as negative controls (N group). The remaining 30 age-matched rats were divided at random into 3 groups: (i) high-fat diet for 5 months starting at age 5 months (H group); (ii) high-fat diet for 5 months starting at age 4 months followed by 1 month of standard chow (H+N1M group); and (iii) high-fat diet for 5 months starting at age 2 months followed by 3 months of standard chow (H+N3M group). All rats underwent erectile function testing and sacrifice at age 10 months. Outcomes: Intracavernous pressure (ICP) and mean arterial pressure (MAP) were measured to evaluate erectile function. Blood samples were collected to measure serum testosterone and lipid levels, and penile tissue specimens were obtained for histological examination. Results: Total body weight, low-density lipoprotein, and serum glucose were significantly higher in the H group compared with the N and H+N3M groups. Serum high-density lipoprotein level was significantly lower in the H group compared with the N and H+N3M groups. The mean ICP/MAP ratio was significantly lower in the H group compared with the N and H+N3M groups (0.33 +/- 0.05 vs 0.79 +/- 0.07 vs 0.73 +/- 0.13; P < .05 for both). Markers for intracorporal neuronal nitric oxide synthase and endothelial cells were more weakly expressed in the H group compared with the N and H+N3M groups. There was no significant difference in smooth muscle content among the groups. Mean cavernosal oxidative stress and the apoptotic index were significantly higher in the H group compared with the N and H+N3M groups. No significant between-group differences were noted with respect to serum testosterone; the H group had significantly higher serum glucose and low-density lipoprotein levels, effects that were partially mitigated in the H+N1M and H+N3M groups. Clinical Translation: Administration of a healthy diet is associated with normalization of functional and histological penile defects associated with a high-fat diet. Strengths & Limitations: Metabolic changes were clearly linked to functional improvements in penile blood flow. Differences between rat and human lipoprotein metabolism are a limitation of this study. Conclusion: Dietary changes may have positive effects on penile hemodynamics in a rat model of hyperlipidemia-associated erectile dysfunction. Copyright (C) 2019, International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.