Increased Na(+)-H+ exchanger activity in the ileal brush-border membrane of spontaneously hypertensive rats.

Abstract

In the present study, we have examined the intestinal Na+ transport, through the Na+)-H+ exchanger in ileal brush-border membrane vesicles (BBMV) isolated from spontaneously hypertensive rats (SHR), and normotensive Wistar Kyoto (WKY) rats as a control group. Na+ uptake into ileal BBMV was stimulated the presence of a proton gradient (pH 5.5 inside/pH 7.5 outside) in SHR and WKY rats, resulting in a transient accumulation (overshoot) in both groups of rats. No overshoot was observed in the absence of a pH gradient. The magnitude of the accumulation was significantly higher in SHR than in WKY rats. Uptake of Na+ at equilibrium was identical in the presence and the absence of a proton gradient and was not changed in SHR. The use of amiloride inhibited pH gradient-driven Na+ uptake in a dose-dependent manner with a Ki of 90 microM and 100 microM for SHR and WKY rats, respectively. The relationship between proton gradient-driven Na+ uptake and external Na+ concentration was saturable and conformed to Michaelis-Menten kinetics in both SHR and WKY rats. Lineweaver-Burk analysis of the pH gradient-driven Na+ uptake indicated values of Vmax that were significantly increased in SHR compared to WKY rats (11.4 +/- 0.55 nmol/mg/8 s vs. 4.96 +/- 0.78 nmol/mg/8 s for SHR and WKY rats, respectively). In contrast, similar K(m) for Na+ were found between SHR and WKY rats (4.0 +/- 0.2 mM vs. 4.9 +/- 0.6 mM for SHR and WKY rats, respectively). These studies show derangement in ileal BBMV Na+ transport of SHR, which is characterized by increased Na(+)-H+ exchanger activity.