Rapid redistribution and inhibition of renal sodium transporters
during natriuresis induced by acute hypertension.
Zhang, Yibin, Austin K. Mircheff, Charles B. Hensley, Clara E. Magyar,
David G. Warnock, Regine Chambrey, Kay-Pong Yip, Donald J. Marsh,
Niels-H. Holstein Rathlou, and Alicia A. McDonough.
Department of Physiology and Biophysics, University of Southern
California School of Medicine, Departments of Medicine and Physiology
and Biophysics, Nephrology Research and Training Center, Vascular
Biology and Hypertension Program, University of Alabama at Birmingham
and Department of Veterans Affairs, Department of Physiology, Brown
University School of Medicine, and University Institute of
Experimental Medicine, Panum Institute, Copenhagen, Denmark
APStracts 3:0023F, 1996.
Acute arterial hypertension provokes a rapid decrease in proximal
tubule sodium reabsorption, increasing flow to the macula densa, the
signal for tubuloglomerular feedback. We tested the hypothesis, in
rats, that sodium transport is decreased due to rapid redistribution
of apical Na/H exchangers and basolateral sodium pumps to internal
membranes. Arterial pressure was increased 50 mm by constricting
various arteries. We also tested whether transporter internalization
occurred when proximal tubule sodium reabsorption was inhibited with
the carbonic anhydrase inhibitor benzolamide. Five min after
initiating either natriuretic stimuli, cortex was removed and
membranes fractionated by density gradient centrifugation. Urine
output and endogenous lithium clearance increased 3 fold in response
to either stimuli. Acute hypertension provoked a redistribution of
apical NHE-3, alkaline phosphatase and dipeptidyl peptidase IV to
higher density membranes enriched in the intracellular membrane
markers. Basolateral membrane Na,K-ATPase activity decreased 50%, 25
-30% of the [alpha]1 and [beta]1 subunits redistributed to higher
density membranes, and the remainder is attributed to decreased
activity of the transporters. Benzolamide did not alter sodium
transporter activity or distribution, implying that decreasing apical
Na+ uptake does not initiate redistribution or inhibition of
basolateral Na,K-ATPase. We conclude that proximal tubule natriuresis
provoked by acute arterial pressure is mediated by both endocytic
removal of apical Na/H exchangers and basolateral sodium pumps as
well as decreased total sodium pump activity.
Received 31 July 1995; accepted in final form 25 January 1996.
APS Manuscript Number F250-5.
Article publication pending Am. J. Physiol. (Renal Fluid Electrolyte
Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 8 February 96