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1 Department of Physiology and Biophysics, University of Southern California School of Medicine, Los Angeles, California, 90033; and 2 Department of Medical Physiology, The Panum Institute, DK-2200 Copenhagen N, Denmark
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-Pi 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 
-/
-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.
basolateral sodium pump; Na/H exchanger isoform 3; Na-Pi cotransporter type 2; membrane trafficking; spontaneously hypertensive rat
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