Aldosterone, mineralocorticoid receptors and vascular inflammation.
For the past 50 years, the physiological action of aldosterone was considered to be on epithelial tissues to maintain fluid and electrolyte homeostasis. Recently, a nonepithelial, pathophysiologic, proinflammatory role for aldosterone has been inferred from studies on mineralocorticoid/salt administration, with or without mineralocorticoid receptor (MR) blockade, in experimental animals, and from clinical studies such as RALES and EPHESUS. More recently still, it has become clear that the pathophysiologic trigger for the vascular inflammatory response observed is not necessarily aldosterone per se, but inappropriate activation of vascular wall MR. MR can be inappropriately activated by aldosterone in the context of an inappropriate salt status, or by glucocorticoids in the context of tissue damage. The studies supporting this latter conclusion, and the novel mechanisms proposed to support this concept, are details in the text to follow.
Funder
John W
JW
Prince Henry's Institute of Medical Research, P.O. Box 5152, Clayton, Victoria 3168, Australia. John.Funder@med.monash.edu.au
D000450:Aldosterone / Q000378:metabolism*; D000818:Animals; D005938:Glucocorticoids / Q000378:metabolism*; D006801:Humans; D000451:Mineralocorticoid Receptor Antagonists / Q000627:therapeutic use; D008901:Mineralocorticoids / Q000378:metabolism*; D018161:Receptors, Mineralocorticoid / Q000378:metabolism*; D014657:Vasculitis / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology*
D005938:Glucocorticoids; D000451:Mineralocorticoid Receptor Antagonists; D008901:Mineralocorticoids; D018161:Receptors, Mineralocorticoid; D000450:Aldosterone