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Am J Physiol Regul Integr Comp Physiol 287: R878-R885, 2004. First published June 17, 2004; doi:10.1152/ajpregu.00180.2004
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WATER AND ELECTROLYTE HOMEOSTASIS

Acute hypotension induced by aortic clamp vs. PTH provokes distinct proximal tubule Na+ transporter redistribution patterns

Patrick K. K. Leong,1 Li E. Yang,1 Harrison W. Lin,1 Niels H. Holstein-Rathlou,2 and Alicia A. McDonough1

1Department of Physiology and Biophysics, University of Southern California Keck School of Medicine, Los Angeles, California 90089-9142; and 2Department of Medical Physiology, Division of Renal and Cardiovascular Research, The Panum Institute, University of Copenhagen, DK-2200 Copenhagen, Denmark

Submitted 18 March 2004 ; accepted in final form 26 May 2004

Renal parathyroid hormone (PTH) action is often studied at high doses (100 µg PTH/kg) that lower mean arterial pressure significantly, albeit transiently, complicating interpretation of studies. Little is known about the effect of acute hypotension on proximal tubule Na+ transporters. This study aimed to determine the effects of acute hypotension, induced by aortic clamp or by high-dose PTH (100 µg PTH/kg), on renal hemodynamics and proximal tubule Na/H exchanger isoform 3 (NHE3) and type IIa Na-Pi cotransporter protein (NaPi2) distribution. Subcellular distribution was analyzed in renal cortical membranes fractionated on sorbitol density gradients. Aortic clamp-induced acute hypotension (from 100 ± 3 to 78 ± 2 mmHg) provoked a 62% decrease in urine output and a significant decrease in volume flow from the proximal tubule detected as a 66% decrease in endogenous lithium clearance. There was, however, no significant change in glomerular filtration rate (GFR) or subcellular distribution of NHE3 and NaPi2. In contrast, high-dose PTH rapidly (<2 min) decreased arterial blood pressure to 51 ± 3 mmHg, decreased urine output, and shifted NHE3 and NaPi2 out of the low-density membranes enriched in apical markers. PTH at much lower doses (<1.4 µg·kg–1·h–1) did not change blood pressure and was diuretic. In conclusion, acute hypotension per se increases proximal tubule Na+ reabsorption without changing NHE3 or NaPi2 subcellular distribution, indicating that trafficking of transporters to the surface is not the likely mechanism; in comparison, hypotension secondary to high-dose PTH blocks the primary diuretic effect of PTH but does not inhibit the PTH-stimulated redistribution of NHE3 and NaPi2 to the base of the microvilli.

kidney; lithium clearance; glomerular filtration rate; blood pressure; rats; parathyroid hormone



Address for reprint requests and other correspondence: A. A. McDonough, Dept. of Physiology and Biophysics, Univ. of Southern California Keck School of Medicine, 1333 San Pablo St., Los Angeles, CA 90089-9142 (E-mail: mcdonoug{at}hsc.usc.edu)




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