Glucocorticoids Promote Na+ Excretion in the Renal Epithelia of Heart Failure Rats by Suppressing Transporter Proteins Involved in Acute Sodium Loading.

Glucocorticoid receptors are essential for normal development and stress responses. Their role in H2O and Na+ metabolism, especially in chronic heart failure (CHF), is not well defined. In a previous study, we found that glucocorticoids potentiate urination in CHF and promote H2O excretion by inhibiting the vasopressin receptor 2 pathway. The present study examines the effect of glucocorticoids on renal Na+ excretion and the underlying mechanisms in CHF rats with acute sodium loading. CHF was induced by left coronary artery ligation for 8 weeks. Rats were randomly assigned to 5 groups: control, CHF, dexamethasone (DEX)-administered CHF, DEX-administered CHF treated with RU486 (mifepristone, a glucocorticoid receptor antagonist), and RU486-treated CHF. An acute sodium loading test was performed 6 hours after DEX administration. Blood and urine samples were collected, and hemodynamics were measured. The expression and localization of Na+ transporter proteins were determined by immunoblotting and immunohistochemistry. DEX increased the urine volume and urinary sodium and improved cardiac function and the estimated glomerular filtration rate in CHF rats. The upregulation of the epithelial sodium channel beta and gamma subunits, Na-K-2Cl cotransporter, serum glucocorticoid-regulated kinase 1 (SGK1), and Na+/K+-ATPase in the renal epithelium of CHF rats was downregulated by DEX. These beneficial effects were abolished by RU486. The expression of natriuretic peptide receptor A was opposite that of the above proteins. Glucocorticoids might induce profound natriuresis in CHF rats during acute sodium loading, which is associated with downregulating some Na+ transporter proteins in the renal epithelium and improving intrarenal hemodynamics.