Aldosterone stimulates surface expression of NHE3 in renal proximal brush borders

The mineralocorticoid aldosterone is one of the major regulators of extracellular volume and blood pressure. It acts by enhancing Na+ reabsorption across tight epithelia such as renal collecting ducts and colon. In addition, it has been shown that aldosterone stimulates NaCl and volume reabsorption in renal proximal tubules by an unknown mechanism. To test the hypothesis that the application of aldosterone results in greater activity of the apical Na+/H+ exchanger-3 (NHE3), we investigated the effect of aldosterone on amiloride-sensitive, proximal tubular volume reabsorption and proximal tubular NHE3 abundance in adrenalectomized rats. Aldosterone at physiological concentrations (dosage 36 mug/100 g b.w. per day) increased NHE3-dependent proximal tubular volume reabsorption and the abundance of NHE3 in brush borders without changing the total amount of NHE3 in cortical homogenates. These results indicate that renal proximal tubular NHE3 is a target for aldosterone-mediated regulation resulting in increased Na+ reabsorption and thus extracellular volume and blood pressure. Further studies are required to determine the precise mechanism of action, especially whether the action of aldosterone on proximal tubular function is direct or indirect.