In addition to demonstrating a remarkable efficacy of MR antagonists to decrease risk of death during heart failure, the Randomized Aldactone Evaluation Study (RALES) study also showed that these effects occur without altering blood pressure.2 Furthermore, spironolactone and eplerenone protected rodents from stroke injury without affecting blood pressure.3,5 However, new information recently has come to light as a result of cell-specific genetic ablation techniques that allow for localization of MR activity key to the pathophysiology of disease. This evidence concerns the gene NR3C2 and heart failure.