Does glucocorticoid receptor blockade exacerbate tissue damage after mineralocorticoid/salt administration?
Mineralocorticoid receptor (MR) antagonism reverses established inflammation, oxidative stress, and cardiac fibrosis in the mineralocorticoid/salt-treated rat, whereas withdrawal of the mineralocorticoid deoxycorticosterone (DOC) alone does not. Glucocorticoid receptors (GRs) play a central role in regulating inflammatory responses but are also involved in cardiovascular homeostasis. Physiological glucocorticoids bind MR with high affinity, equivalent to that for aldosterone, but are normally prevented from activating MR by pre-receptor metabolism by 11beta-hydroxysteroid dehydrogenase 2. We have previously shown a continuing fibrotic and hypertrophic effect after DOC withdrawal, putatively mediated by activation of glucocorticoid/MR complexes; the present study investigates whether this effect is moderated by antiinflammatory effects mediated via GR. Uninephrectomized rats, drinking 0.9% saline solution, were treated as follows: control; DOC (20 mg/wk) for 4 wk; DOC for 4 wk and no st
