REVERSIBLE EFFECTS OF ACUTE HYPERTENSION ON PROXIMAL TUBULE SODIUM TRANSPORTERS

Acute hypertension provokes a rapid decrease in proximal tubule sodium reabsorption with a decrease in basolateral membrane sodium-potassium -ATPase activity and an increase in the density of membranes containin g apical membrane sodium/hydrogen exchangers (NHE3) [Y. Zhang, A. K. M ircheff, C. B. Hensley, C. E. Magyar, D. G. Warnock, R. Chambrey, K.-P . Yip, D. J. Marsh, N.-H. Holstein-Rathlou, and A. A. McDonough. Am. J . Physiol. 270 (Renal Fluid Electrolyte Physiol. 39): F1004-F1014, 199 6]. To determine the reversibility and specificity of these responses, rats were subjected to 1) elevation of blood pressure (BP) of 50 mmHg for 5 min, 2) restoration of normotension after the first protocol, o r 3) sham operation. Systolic hypertension increased urine output and endogenous lithium clearance three- to fivefold within 5 min, but thes e returned to basal levels only 15 min after BP was restored. Renal co rtex lysate was fractionated on sorbitol gradients. Basolateral membra ne sodium-potassium-ATPase activity (but not subunit immunoreactivity) decreased one-third to one-half after BP was elevated and recovered a fter BP was normalized. After BP was elevated, 55% of the apical NHE3 immunoreactivity, smaller fractions of sodium-phosphate co-transporter immunoreactivity, and apical alkaline phosphatase and dipeptidyl-pept idase redistributed to membranes of higher density enriched in markers of the intermicrovillar cleft (megalin) and endosomes (Rab 4 and Rab 5), whereas density distributions of the apical cytoskeleton protein v illin were unaltered. After 20 min of normalized BP, all the NHE3 and smaller fractions of the other apical membrane proteins returned to th eir original distributions. These findings suggest that the dynamic re gulation of proximal tubule sodium transport by acute changes in BP ma y be mediated by rapid reversible regulation of sodium pump activity a nd relocation of apical sodium transporters.