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.

Diversity of the mammalian sodium/proton exchanger SLC9 gene family

“…Aberrant NHE3 activity has been implicated as a potential contributing factor in the pathophysiology of other disease states, including hypertension and renal ischemia-reperfusion injuries. Isolated ileum [141] and renal proximal tubules [62] of spontaneously hypertensive rats (SHR) show increased levels of NHE3 activity and protein in brush-border membranes compared with control Wistar-Kyoto (WKY) animals, which may contribute to increased Na + reabsorption and the pathogenesis of hypertension. Similarly, induction of diabetes mellitus in rats-a disease associated with hypertension and renal dysfunction-increases renal brush-border NHE3 activity, which reverses upon insulin treatment [54].…”

Regulation of sodium-glucose cotransporter SGLT1 in the intestine of hypertensive rats

“…These reports have described inhibition of active sodium transport (26), and increased passive membrane permeability for sodium in essential hypertension (5). In spontaneously hypertensive rats (SHR), a classical experimental model for the study of hypertension, stimulation of Na ϩ /H ϩ exchanger has been shown compared with their normotensive genetic control, Wistar-Kyoto (WKY) rats (58). Furthermore, similar changes in sodium transport have been found in other hypertensive models, such as Dahl salt-sensitive rats (30,32), Milan hypertensive rats (48), and fructose-fed rats (9).…”

Gastrointestinal–Renal Axis: Role in the Regulation of Blood Pressure

“…Increased intestinal sodium absorption is associated with increased blood pressure in elderly humans . However, NHE activity is increased in the jejunum and ileum of younger (6–9 weeks) but not older (12 weeks) spontaneously hypertensive rats . NHE2, NHE3, and NHE8 are found at the brush border membrane of the small intestinal epithelium.…”

“…64 However, NHE activity is increased in the jejunum and ileum of younger (6-9 weeks) but not older (12 weeks) spontaneously hypertensive rats. 65,66 NHE2, NHE3, and NHE8 are found at the brush border membrane of the small intestinal epithelium. Studies in Nhe2 À/À and Nhe3 À/À mice have demonstrated that NHE3 accounts for most of the neutral NaCl absorption in the small intestine.…”