Laboratory Investigation

Kidney International (1989) 36, 576–581; doi:10.1038/ki.1989.233

Increased Na+/H+ antiport activity in the renal brush border membrane of SHR

Gabriel A Morduchowicz, David Sheikh-Hamad, Ok D Jo, Edward P Nord, David B N Lee and Norimoto Yanagawa

Division of Nephrology, Medical and Research Services, Veterans Administration Sepulveda Hospital, Sepulveda, and Division of Nephrology, Department of Medicine, University of California at Los Angeles, School of Medicine, Los Angeles, California, USA

Correspondence: Norimoto Yanagawa MD, Nephrology Division (111R), Sepulveda Veterans Administration Medical Center, 16111 Plummer Street, Sepulveda, California 91343, USA.

Received 31 May 1988; Revised 2 March 1989; Accepted 16 May 1989.

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Abstract

Increased Na+/H+ antiport activity in the renal brush border membrane of SHR. Defect in renal salt excretion may play an important role in the pathogenesis of hypertension. We examined sodium (Na+) uptake by brush border membrane (BBM) vesicles of young (6 week old) spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY) of the same age. SHR had lower urinary Na+ excretion (223.1 plusminus 9.3 vs. 266.3 plusminus 3.7 microEq/day/lOO g, N = 8, P < 0.01) and higher systolic blood pressure (98.9 plusminus 1.2 vs. 82.9 plusminus 1.8 mm Hg, N = 8, P < 0.01) than WKY. BBM vesicle Na+ uptake, measured by rapid filtration technique, was higher in SHR when compared to WKY (1.44 plusminus 0.03 vs. 1.01 plusminus 0.06 nmol/mg/5 sec, N = 4, N < 0.01). This increase in Na+ influx was apparent only in the present of an outward-directed proton (H+) gradient and was abolished by 1 mM amiloride. BBM permeability to H+ as assessed by acridine orange quenching was not different between SHR and WKY. Kinetic analyses of the amiloride-sensitive BBM Na+ uptake revealed a higher Vmax (2.13 plusminus 0.27 vs. 0.70 plusminus 0.30 nmol/mg/5 sec, N = 4, P < 0.01) and a higher km for Na+ (3.55 plusminus 0.32 vs. 1.23 plusminus 0.14 mM, N = 4, P < 0.05) in SHR. These findings thus demonstrate an intrinsic derangement in BBM Na+ transport in young SHR which is characterized by increased Na+/H+ antiport activity. This alteration in antiport activity is not attributable to changes in membrane permeability to H+, and is characterized by higher Vmax and km. Similar reports of increased Na+/H+ antiport activity in other tissues of SHR suggest that a generalized membrane transport disorder may exist in this model of genetic hypertension.

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