The spontaneously hypertensive rats and their genetically matched controls, Wistar-Kyoto, serve as models of essential hypertension. The present study was undertaken to determine whether brush border membrane vesicles obtained from jejunal enterocytes of spontaneously hypertensive rats show increased Na+-H+ exchange as part of a generalized membrane disorder. Brush border membrane vesicles were prepared from the jejunum of adult spontaneously hypertensive rats and Wistar-Kyoto rats using an Mg2+/ethylene glycol tetraacetic acid precipitation method. Uptake of 22Na by these vesicles was found to be into an osmotically sensitive intravesicular space rather than mere binding. Initial Na+ uptake by brush border membrane vesicles was greater in spontaneously hypertensive rats than in Wistar-Kyoto rats (P < 0.05). Higher total and amiloride-sensitive Na+ uptake in spontaneously hypertensive rats occurred in the presence of an outwardly directed pH gradient, and uptake became statistically similar to that of Wistar-Kyoto rats in the absence of a pH gradient. Moreover, amiloride-insensitive Na+ uptake under an outwardly directed pH gradient did not differ significantly between the two groups. The enhanced Na+-H+ activity in spontaneously hypertensive rats is not due to altered membrane permeability to protons, as is shown by acridine orange-quenching studies. Kinetic studies for amiloride-sensitive Na+ uptake showed a greater Vmax in spontaneously hypertensive rats compared with Wistar-Kyoto rats (1.46 ± 0.05 vs. 1.08 ± 0.08 nmol · mg protein-1 · 7 s-1) but the Km values were similar in the two groups. These findings, along with similar findings previously reported in vascular smooth muscle and renal tissue of SHR, strongly suggest that an increased Na+-H+ exchange is related to the development of hypertension.
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