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) out of the brush border into higher density membranes, and inhibition of renal 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 persistent adaptive changes in NHE3 and NaPi2 distribution and/or NKA activity. Renal cortex Na transporter protein density distributions and activities were compared by subcellular fractionation in 1) adult SHR with an acute increase or decrease in arterial pressure and 2) young SD (YSD) and young SHR (YSHR) vs. adult SD and SHR. In adult hypertensive SHR NHE3 was shifted to membranes of higher densities, analogous to SD with acute hypertension, and there 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 peptidase IV (DPPIV), 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 40% greater in YSHR than YSD and decreased to SD levels in adults. We conclude that there are persistent changes in Na(+) transporter distributions and activity in response to chronic hypertension in SHR that mimic the responses to acute hypertension seen in SD rats and that elevated sodium pump activity per transporter in YSHR may contribute to the generation of hypertension.
Department of Physiology and Biophysics, University of Southern California School of Medicine, Los Angeles 90033, USA.
C E
CE
Magyar
Y
Y
Zhang
N H
NH
Holstein-Rathlou
A A
AA
McDonough
D000208:Acute Disease; D000375:Aging / Q000502:physiology; D000818:Animals; D001794:Blood Pressure; D002352:Carrier Proteins / Q000378:metabolism*; D002908:Chronic Disease; D006973:Hypertension / Q000201:enzymology / Q000378:metabolism* / Q000503:physiopathology; D007687:Kidney Tubules, Proximal / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D051381:Rats; D011918:Rats, Inbred SHR; D017207:Rats, Sprague-Dawley; D000074083:Sodium-Hydrogen Exchanger 3; D017923:Sodium-Hydrogen Exchangers / Q000378:metabolism*; D050608:Sodium-Phosphate Cotransporter Proteins; D050610:Sodium-Phosphate Cotransporter Proteins, Type II; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D013045:Species Specificity; D027981:Symporters; D014018:Tissue Distribution
D002352:Carrier Proteins; C000613387:Slc9a3 protein, rat; D000074083:Sodium-Hydrogen Exchanger 3; D017923:Sodium-Hydrogen Exchangers; D050608:Sodium-Phosphate Cotransporter Proteins; D050610:Sodium-Phosphate Cotransporter Proteins, Type II; D027981:Symporters; D000254:Sodium-Potassium-Exchanging ATPase