The aldosterone receptor--new insights?

Aldosterone, or mineralocorticoid, excess plays an important role in the pathophysiology of cardiac disease. This response is mediated through the mineralocorticoid receptor (MR). Although blockade of the MR has been shown to reduce mortality in cardiac failure, therapy may be limited by the hyperkalaemia that results from blockade of the renal MR. It is now well established for a number of steroid receptors that tissue-specific antagonism and agonism can be achieved by the so-called selective receptor modulators. Recently, three groups have crystallised the ligand-binding pocket of the MR, and each reveal a structure that is similar to that of the other steroid receptors. This raises the possibility that cardiac-specific antagonists of the MR may be developed that avoid the potassium retention seen with blockade of the renal MR.