Effects of mineralocorticoid receptor blockade on glucocorticoid-induced renal injury in adrenalectomized rats

Kazi Rafiq, Daisuke Nakano, Genei Ihara, Hirofumi Hitomi, Yoshihide Fujisawa, Naro Ohashi, Hiroyuki Kobori, Yukiko Nagai, Hideyasu Kiyomoto, Masakazu Kohno, Akira Nishiyama

Research output: Contribution to journalArticlepeer-review

39 Citations (Scopus)

Abstract

Objectives: Aldosterone is well recognized as the selective physiological ligand for mineralocorticoid receptor in epithelia. However, in-vitro studies have demonstrated that the affinity of aldosterone and glucocorticoids for mineralocorticoid receptor is similar. We hypothesized that glucocorticoids are involved in the development of renal injury through an mineralocorticoid receptor-dependent mechanism. METHODS AND Results: Uninephrectomized (UNX) rats were treated with 1% NaCl and divided into three groups: vehicle, bilateral adrenalectomy (ADX) + hydrocortisone (HYDRO; 5 mg/kg/day, s.c.), ADX + HYDRO + eplerenone (0.125% in chow). HYDRO-treated UNX-ADX rats showed increased blood pressure and urinary albumin-to-creatinine ratio with an increase in the expression of the mineralocorticoid receptor target genes, serum and glucocorticoid-regulated kinases-1 and Na/H exchanger isoform-1, in renal tissues. HYDRO treatment induced morphological changes in the kidney, including glomerulosclerosis and podocyte injury. Treatment with eplerenone markedly decreased the gene expression and reduced the albuminuria and renal morphological changes. In contrast, dexamethasone (0.2 mg/kg per day, s.c.) + UNX + ADX induced hypertension and albuminuria in different groups of rats. Eplerenone failed to ameliorate these changes. Conclusions: Our findings indicate that chronic glucocorticoid excess could activate mineralocorticoid receptor and, in turn, induce the development of renal injury.

Original languageEnglish
Pages (from-to)290-298
Number of pages9
JournalJournal of hypertension
Volume29
Issue number2
DOIs
Publication statusPublished - 2011 Feb

Keywords

  • eplerenone
  • hydrocortisone
  • kidney diseases
  • mineralocorticoid receptor

ASJC Scopus subject areas

  • Internal Medicine
  • Physiology
  • Cardiology and Cardiovascular Medicine

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