Recent reports showed an unexpected worsening of endothelial function by aldosterone antagonism in diabetic patients, suggesting that aldosterone could interfere with the detrimental consequences of diabetes on microvasculature and thus on cardiac function.

To test this hypothesis, diabetes (D) was induced in male mice overexpressing the aldosterone synthase in heart (Tg) and in wildtype ones (Wt) by streptozotocin. Eight weeks after streptozotocin injection, impairment of left ventricular systolic function parameters measured by echocardiography (fraction of shortening) was accompanied by a decrease in capillaries/cardiomyocyte ratio (−20 %) and VEGFa expression (−40 %) in Wt-D mice compared with normoglycemic littermates. Furthermore, Wt-D mice demonstrated an increase of superoxide production (+100 %) and proteins carbonylation (+33 %), hallmarks of oxidative stress. Apart a slight increase of proteins carbonylation, all these diabetes-associated cardiac alterations were undetectable in Tg-D mice. Note that fibrosis was induced similarly in both diabetic groups. Eplerenone (aldosterone antagonist) abolished all the effects of aldosterone synthase overexpression, but had no effects in Wt-D mice.

By preventing VEGFa down-regulation through a mineralocorticoid receptor-dependent mechanism, aldosterone prevents systolic dysfunction by maintaining capillary density. Understanding how aldosterone prevents VEGFa down-regulation in experimental diabetic cardiomyopathy could be of importance to define new strategies targeting the prevention of capillary rarefaction.