RAPID REDISTRIBUTION AND INHIBITION OF RENAL SODIUM TRANSPORTERS DURING ACUTE PRESSURE NATRIURESIS

Acute arterial hypertension provokes a rapid decrease in proximal tubu le (PT) Nai reabsorption, increasing flow to the macula densa, the sig nal for tubuloglomerular feedback. We tested the hypothesis, in rats, that Na+ transport is decreased due to rapid redistribution of apical Na+/H+ exchangers and basolateral Na+ pumps to internal membranes. Art erial pressure was increased 50 mmHg by constricting various arteries. We also tested whether transporter internalization occurred when PT N a+ reabsorption was inhibited with the carbonic anhydrase inhibitor be nzolamide. Five minutes after initiating either natriuretic stimuli, c ortex was removed, and membranes were fractionated by density gradient centrifugation. Urine output and endogenous lithium clearance increas ed threefold in response to either stimuli. Acute hypertension provoke d a redistribution of apical Na+/H+ exchanger NHE3, alkaline phosphata se, and dipeptidyl peptidase IV to higher density membranes enriched i n the intracellular membrane markers. Basolateral membrane Na+-K+-aden osinetriphosphatase (Na+-K+-ATPase) activity decreased 50%, 25-30% of the alpha(1)- and beta(1)-subunits redistributed to higher density mem branes, and the remainder is attributed to decreased activity of the t ransporters. Benzolamide did not alter Na+ transporter activity or dis tribution, implying that decreasing apical Na+ uptake does not initiat e redistribution or inhibition of basolateral Na+-K+-ATPase. We conclu de that PT natriuresis provoked by acute arterial pressure is mediated by both endocytic removal of apical Na+/H+ exchangers and basolateral Na+ pumps as well as decreased total Na+ pump activity.