title: Steroids, hypertension and cardiac fibrosis.
abstract: Though we normally think of mineralocorticoid receptors as mediating aldosterone action on the kidney and other epithelia, the same receptors are found at comparable levels in non-epithelial tissues such as hippocampus and heart. In all tissues mineralocorticoid receptors have identical, high affinity for aldosterone, corticosterone and cortisol. In tissues such as the heart and hippocampus they are unprotected by the enzyme 11 beta hydroxysteroid dehydrogenase, which converts glucocorticoids to inactive 11-keto congeners; in such tissues mineralocorticoid receptors are thus overwhelmingly occupied by glucocorticoids, reflecting their much higher circulating levels. The epithelial effects of mineralocorticoid receptors and glucocorticoid receptors appear relatively uncomplicated, paralleling findings in cotransfection systems (corticosterone and cortisol, as well as aldosterone, are agonist in mineralocorticoid receptors; activated mineralocorticoid receptors and activated glucocorticoid receptors equivalently transactivate gene expression). In non-epithelial tissues, most notably the brain, the actions (and possible interactions) of mineralocorticoid receptors and glucocorticoid receptors appear much more complex, and are yet to be established in detail. We have recently confirmed and extended the findings of Weber and his colleagues that administration of aldosterone or deoxycorticosterone to uninephrectomized rates drinking 1% NaCl solution for 8 weeks is followed by interstitial and perivascular cardiac fibrosis. Whether or not the effect of corticosteroids on cardiac fibrosis reflects direct actions on cardiac muscle, or other cellular constituents of the heart, there appears to be significant interplay between mineralocorticoid receptors and glucocorticoid receptors, and possible roles for agonist and antagonist occupancy of both receptor types.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Baker Medical Research Institute, Melbourne, Australia.
authors.forename: J W
authors.initials: JW
authors.lastname: Funder
mesh_terms: D000818:Animals; D004719:Endomyocardial Fibrosis / Q000139:chemically induced* / Q000503:physiopathology; D006801:Humans; D006973:Hypertension / Q000139:chemically induced* / Q000503:physiopathology; D018161:Receptors, Mineralocorticoid / Q000378:metabolism / Q000502:physiology; D013256:Steroids / Q000494:pharmacology / Q000502:physiology / Q000633:toxicity*
chemical_list: D018161:Receptors, Mineralocorticoid; D013256:Steroids