Differential Regulation of Na+ Transporters along Nephron during AngII-Dependent Hypertension: Distal Stimulation Counteracted by Proximal Inhibition.

This study tests the hypothesis that Ang II infusion activates Na(+) transporters in the distal nephron while inhibiting transporters along the proximal nephron. Male Sprague-Dawley rats were infused with AngII (400 ng/kg/min) or vehicle for 2 weeks. Kidneys were dissected (cortex versus medulla) or fixed for immunohistochemistry (IHC). AngII increased mean arterial pressure by 40 mmHg, urine Na(+) by 1.67-fold, and urine volume by 3-fold, evidence for hypertension and pressure natriuresis. Na(+) transporters' abundance and activation (assessed by phosphorylation (-P) or proteolytic cleavage), were measured by immunoblot. During AngII infusion: Na(+)/H(+) exchanger 3 (NHE3) abundance decreased in both cortex and medulla; Na-K-2Cl cotransporter 2 (NKCC2) decreased in medullary thick ascending loop of Henle (TALH) and increased, along with NKCC2-P, in cortical TALH; Na-Cl cotransporter (NCC) and NCC-P increased in the distal convoluted tubule; epithelial Na(+) channel subunits and their cleaved forms were increased in both cortex and medulla. Like NKCC2, STE20/SPS1-related proline alanine-rich kinase (SPAK) and SPAK-P were decreased in medulla and increased in cortex. By IHC, during Ang II: NHE3 remained localized to PT microvilli at lower abundance and the differential regulation of NKCC2 and NKCC2-P in cortex versus medulla was evident. In summary, AngII-infusion increases Na(+) transporter abundance and activation from cortical TALH to medullary collecting duct while the hyp...
Source: Am J Physiol Renal P... - Category: Urology & Nephrology Authors: Tags: Am J Physiol Renal Physiol Source Type: research