The Obese Zucker Rat is Not a Model of Obesity‐Associated Pulmonary Hypertension

Abstract

Obesity is often associated with the development of pulmonary hypertension and right-heart failure. The increased pulmonary vascular resistance is associated with elevated vasoconstriction and arterial medial thickening. To date, normal lean animals exposed to intermittent bouts of hypoxia, mimicking sleep apnea, have been used as a model of obesity-associated pulmonary hypertension. This model ignores the milieu of metabolic abnormalities associated with obesity, which may play a role in the pulmonary hypertension associated with obesity. The obese Zucker rat exhibits obesity, Type 2 diabetes, and systemic hypertension. Therefore we hypothesized that the obese Zucker rat would be an ideal model of obesity-associated pulmonary hypertension. To this end, small pulmonary arterial vasoconstrictor reactivity, medial hypertrophy, and right ventricular weight were determined in male 16–18 wk old lean and obese Zucker rats. Vasoconstrictor reactivity to Uridine 5′ triphosphate in small pulmonary arteries was similar between lean and obese rats. Contrary to our hypothesis medial wall thickness was significantly thinner in 20–60 μm arterioles from obese animals as compared to lean animals. For 60–100 μm and 100–200 μm arterioles, there were no significant differences in medial wall thickness between groups. The right ventricular/total heart weight ratio was similar between groups. These results suggest that the obese Zucker rat may not be an appropriate model for obesity-associated pulmonary hypertension. This work was supported by NIH F32HL082438 and NIH HL-51971 and HL 63958