Brain mineralocorticoid receptors: orchestrators of hypertension and end-organ disease.
OBJECTIVE
'New' tasks have been discovered for aldosterone and its receptor, the mineralocorticoid receptor, within both epithelial tissues of vectorial ion and water transport, such as the kidney, and non-epithelial organs, including the brain, heart and vessels. Promising results of clinical trials using low doses of mineralocorticoid receptor antagonists to forestall end-organ disease is resulting in an increase in their use, yet the biology of the mineralocorticoid receptor is far from clear.


RESULTS
Mineralocorticoid receptors within the kidney, heart and blood vessels mediate direct effects of aldosterone, including tissue inflammation, hypertrophy and fibrosis, that are independent of blood pressure. Activation, by aldosterone, of mineralocorticoid receptors in the brain increases central sympathetic nervous system drive to the periphery, thereby producing hypertension through multiple mechanisms, and increases levels of proinflammatory cytokines in both the circulation and peripheral tissues. Blocking of the mineralocorticoid receptor of the forebrain lowers the levels of peripheral tissue cytokines, including those induced by ischemic injury in the heart. Aldosterone is produced within the heart, blood vessels and brain, potentially liberating regulation of local concentrations of the steroid from peripheral mechanisms of control. A conundrum yet to be explained is the ligand-dependent functional specificity of the mineralocorticoid receptor in some non-epithelial tissues, which may be crucial to our understanding the end-organ pathophysiology of hypertension.


CONCLUSIONS
New technology is rapidly adding layers of complexity to, rather than simplifying, our understanding of the facile terms 'hemodynamic homeostasis' and 'end-organ' disease, but within this new knowledge lies the promise of better, more precise treatment of hypertension and its sequelae.
Gomez-Sanchez
Elise P
EP
Division of Endocrinology, University of Mississippi Medical Center, Jackson, Mississippi 39216, USA. egomez-sanchez@medicine.umsmed.edu
D000450:Aldosterone / Q000378:metabolism*; D001921:Brain; D004194:Disease / Q000209:etiology*; D006321:Heart; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000503:physiopathology*; D007668:Kidney; D018161:Receptors, Mineralocorticoid / Q000502:physiology*
D018161:Receptors, Mineralocorticoid; D000450:Aldosterone