Fig. 3.

A hypothesis for MR activation and its blockade in the setting of reduced RAAS. Selective MR blockade with eplerenone attenuates cardiac remodeling and failure as well as coronary vascular inflammation, independent of its antihypertensive effect, in rats with salt-sensitive hypertension. The expression of 11β-HSD1 gene is upregulated, 11β-HSD2 and CYP11B1 genes are expressed at only minimal levels, and the expression of CYP11B2 gene is not detected in the hearts of such rats. Corticosterone, an endogenous glucocorticoid in rodents, manifests the same affinity for the MR as does aldosterone. Glucocorticoid-mediated MR activation may thus contribute to cardiac and coronary vascular injury in this model of low-renin, low-aldosterone hypertension. Increased oxidative stress appears to be a driver for activation of the glucocorticoid-MR complex in the cardiovascular system of these animals.

Abbreviations: MR, mineralocorticoid receptor; RAAS, renin-angiotensin-aldosterone system; 11β-HSD1 and 2, 11β-hydroxysteroid dehydrogenase types 1 and 2, respectively; GRE, glucocorticoid response element.