Background: 

Aldosterone plays a crucial role in cardiovascular disease. Its effects are well documented in the heart, where mineralocorticoid receptor (MR) antagonists reduce mortality in patients with congestive heart failure. In the vasculature, MR antagonism decreases atherosclerosis and restores endothelial function by reducing inflammation and oxidative stress. Obesity is associated with increased plasma aldosterone levels. In addition, adipose tissue has been shown to be a major source of aldosterone and a stimulus of its secretion.

Aim: 

The goal of our study was to understand the role of aldosterone in the context of obesity-induced vascular disease using a mouse model of diet-induced obesity.

Methods and Results: 

We exposed 6 weeks old male C57BL/6J mice to 14 weeks of high-fat diet (60% lard) or normal chow diet. Obese mice developed a prediabetic state (impaired glucose tolerance) as well as impaired endothelial function (organ chambers) compared with lean mice. Plasma aldosterone levels as well as expression of aortic MR were increased in obese mice.

Conclusions and Perspectives: 

Diet-induced obesity impairs glucose tolerance and endothelial function; it increases plasma aldosterone levels and aortic MR expression. Our next experiments will focus on aldosterone-mediated endothelial cell RNA expression and on the effects of chronic pharmacological MR blockade.