Proximal tubule Na transporter responses are the same during acute and chronic hypertension

Acute hypertension in Sprague-Dawley rats (SD) provokes a decrease in renal proximal tubule (PT) salt and fluid reabsorption, redistribution of apical Na/H exchanger isoform 3 (NHE3) and Na-P-i cotransporter type 2 (NaPi2) ou t of the brush border into higher density membranes, and inhibition of rena l cortical Na-K-ATPase (NKA) activity (41). The aims of this study were to determine 1) whether an increase in arterial pressure affects distribution or activity of Na transporters in the spontaneously hypertensive rat (SHR) and 2) whether development of chronic hypertension in SHR leads to persiste nt adaptive changes in NHE3 and NaPi2 distribution and/or NKA activity. Ren al cortex Na transporter protein density distributions and activities were compared by subcellular fractionation in 1) adult SHR with an acute increas e or decrease in arterial pressure and 2) young SD (YSD) and young SHR (YSH R) vs. adult SD and SHR. In adult hypertensive SHR NHE3 was shifted to memb ranes of higher densities, analogous to SD with acute hypertension, and the re were no further changes with a further increase or decrease in arterial pressure. There was no change in total pool size of NHE3 in cortex in YSHR vs. SHR. NHE3, NaPi2, megalin, NKA alpha-/beta-subunit, dipeptidyl peptidas e IV (DP-PIV), and villin distributions were the same in YSHR vs. YSD. NHE3 , NaPi2, and megalin shifted to higher densities in adult SHR, but not SD, with age. Basolateral NKA and apical alkaline phosphatase activities were 4 0% greater in YSHR than YSD and decreased to SD levels in adults. We conclu de that there are persistent changes in Na+ transporter distributions and a ctivity in response to chronic hypertension in SHR that mimic the responses to acute hypertension seen in SD rats and that elevated sodium pump activi ty per transporter in YSHR may contribute to the generation of hypertension .