(065) Characterization of Cardiovascular Function, Metabolic Status and Erectile Function in Preclinical Model of Cardiometabolic Syndrome
Authors: Pallas W , Hannan J 
Published: February 2024

Abstract

Introduction
Cardiometabolic syndrome is a widespread health issue and common cause of erectile dysfunction (ED). Cardiometabolic syndrome encompasses a group of indications including abdominal obesity, insulin-resistant glucose metabolism, dyslipidemia, and hypertension. To date, studies have looked at high fructose or high fat diets to induce cardiometabolic syndrome and ED in rodents, but these models do not closely model the clinical phenotype. Furthermore, the molecular basis of ED in cardiometabolic syndrome needs to be elucidated.

Objective
Our objective is to characterize the cardiovascular and erectile function, and metabolic status in the ZSF-1 obese rat. This hybrid rat is a cross between a Zucker diabetic fatty female and a spontaneously hypertensive heart failure male rat. We hypothesize that with age the ZSF-1 obese rats will demonstrate similar disease phenotype as seen clinically and develop ED.

Methods
We used male lean and obese ZSF-1 rats (n=8/group). We measured body weight weekly, and performed apomorphine erectile testing, MRI to assess body composition and glucose tolerance tests at 10, 20, 30 weeks. At 30 weeks, we assessed erectile function using ICP/MAP and vascular stiffness was measured via laser doppler pulse wave velocity (PWV). Additionally, acetylcholine (Ach)-mediated vasodilation, vasodilation to sodium nitroprusside (SNP), and contraction to phenylephrine (PE) was measured in thoracic and abdominal aortas. Aorta and penile segments were collected for histological analyses.

Results
On average, obese rats were 60% larger (230g) than controls, had greater percent body fat and had significantly impaired glucose tolerance at all time points (p&lt;0.05). Over time, ZSF-1 obese rats developed ED as there was a significant decrease in apomorphine-induced erections by 30 weeks (p&lt;0.05). ED was confirmed by significantly reduced ICP/MAP in ZSF-1 obese compared to lean rats (p&lt;0.05). Obese rats were significantly more hypertensive compared to lean rats (MAP: 140.2 mmHg vs 99.6mmHg, p&lt;0.05). Lean and obese rats had no difference in vascular stiffness indicated by PWV. In our tissue bath experiments, ACh-mediated vasodilation was significantly decreased in the thoracic aorta of obese rats (p&lt;0.05) while the abdominal aorta was unchanged. SNP-mediated vasodilation was similar between groups in both thoracic and abdominal aortas. At high concentrations, PE-mediated vasoconstriction was significantly increased in the thoracic and decreased in the abdominal aortas of obese rats (p&lt;0.05).

Conclusions
To our knowledge, this is the first report on the erectile function in the ZSF-1 rat model of cardiometabolic syndrome. The ZSF-1 obese rats had marked adiposity, hypertension, hyperglycemia and presented with aortic endothelial dysfunction and ED. We are currently assessing testosterone levels and penile fibrosis. We believe that the ZSF-1 rat is useful for studying ED as they gradually develop metabolic disease and ED over time like the human disease.

Disclosure
No.