Short-term nonpressor angiotensin II infusion stimulates sodium transporters in proximal tubule and distal nephron.
In Sprague Dawley rats, 2-week angiotensin II (AngII) infusion increases Na(+) transporter abundance and activation from cortical thick ascending loop of Henle (TALH) to medullary collecting duct (CD) and raises blood pressure associated with a pressure natriuresis, accompanied by depressed Na(+) transporter abundance and activation from proximal tubule (PT) through medullary TALH. This study tests the hypothesis that early during AngII infusion, before blood pressure raises, Na(+) transporters' abundance and activation increase all along the nephron. Male Sprague Dawley rats were infused via osmotic minipumps with a subpressor dose of AngII (200 ng/kg/min) or vehicle for 3 days. Overnight urine was collected in metabolic cages and sodium transporters' abundance and phosphorylation were determined by immunoblotting homogenates of renal cortex and medulla. There were no significant differences in body weight gain, overnight urine volume, urinary Na(+) and K(+) excretion, or rate of excretion of a saline challenge between AngII and vehicle infused rats. The 3-day nonpressor AngII infusion significantly increased the abundance of PT Na(+)/H(+) exchanger 3 (NHE3), cortical TALH Na-K-2Cl cotransporter 2 (NKCC2), distal convoluted tubule (DCT) Na-Cl cotransporter (NCC), and cortical CD ENaC subunits. Additionally, phosphorylation of cortical NKCC2, NCC, and STE20/SPS1-related proline-alanine-rich kinase (SPAK) were increased; medullary NKCC2 and SPAK were not altered. In conclusion, 3-day AngII infusion provokes PT NHE3 accumulation as well as NKCC2, NCC, and SPAK accumulation and activation in a prehypertensive phase before evidence for intrarenal angiotensinogen accumulation.
Department of Cell and Neurobiology, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.
Mien T X
MT
Nguyen
Department of Cell and Neurobiology, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.
Jiyang
J
Han
Department of Cell and Neurobiology, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.
Donna L
DL
Ralph
Department of Cell and Neurobiology, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.
Luciana C
LC
Veiras
Department of Cell and Neurobiology, Keck School of Medicine, University of Southern California, Los Angeles, California, USA mcdonoug@usc.edu.
Alicia A
AA
McDonough
ENaC; NCC; NHE3; NKCC2; SPAK; intrarenal RAS