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

TY - JOUR

T1 - Acute hypotension induced by aortic clamp vs. PTH provokes distinct proximal tubule Na+ transporter redistribution patterns.

AU - Leong, Patrick K K

AU - Yang, Li E

AU - Lin, Harrison W

AU - McDonough, Alicia A

AU - Holstein-Rathlou, N.-H.

N1 - Keywords: Animals; Aorta, Thoracic; Carrier Proteins; Centrifugation, Density Gradient; Constriction; Cyclic AMP; Dose-Response Relationship, Drug; Glomerular Filtration Rate; Hypotension; Immunoblotting; Kidney Function Tests; Kidney Tubules, Proximal; Male; Parathyroid Hormone; Rats; Rats, Sprague-Dawley; Renal Circulation; Sodium; Sodium-Hydrogen Antiporter; Sodium-Phosphate Cotransporter Proteins; Sodium-Phosphate Cotransporter Proteins, Type IIa; Symporters

PY - 2004

Y1 - 2004

N2 - Renal parathyroid hormone (PTH) action is often studied at high doses (100 microg 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 microg PTH/kg), on renal hemodynamics and proximal tubule Na/H exchanger isoform 3 (NHE3) and type IIa Na-P(i) 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 microg.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.

AB - Renal parathyroid hormone (PTH) action is often studied at high doses (100 microg 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 microg PTH/kg), on renal hemodynamics and proximal tubule Na/H exchanger isoform 3 (NHE3) and type IIa Na-P(i) 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 microg.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.

U2 - 10.1152/ajpregu.00180.2004

DO - 10.1152/ajpregu.00180.2004

M3 - Journal article

C2 - 15205183

SN - 0363-6119

VL - 287

SP - R878-85

JO - American Journal of Physiology - Regulatory Integrative and Comparative Physiology

JF - American Journal of Physiology - Regulatory Integrative and Comparative Physiology

IS - 4

ER -