Potassium Supplementation Prevents Sodium Chloride Cotransporter Stimulation During Angiotensin II Hypertension

Abstract

Ang II hypertension increases distal tubule Na-Cl cotransporter (NCC) abundance and phosphorylation (NCCp), as well as epithelial Na+ channel (ENaC) abundance and activating cleavage. Acutely raising plasma [K+] by infusion or ingestion provokes a rapid decrease in NCCp that drives a compensatory kaliuresis. The first aim tested whether acutely raising plasma [K+] with a single 3 hr 2% potassium meal would lower NCCp in Sprague Dawley rats after 14 days of AngII (400 ng/kg/min). The potassium-rich meal neither decreased NCCp nor increased K+ excretion. AngII infused rats exhibited lower plasma [K+] versus controls (3.6 ± 0.2 vs. 4.5 ± 0.1 mmol/L, p < 0.05) suggesting that Ang II mediated ENaC activation provokes K+ depletion. The second aim tested whether doubling dietary potassium intake from 1% (A1K) to 2% (A2K) would prevent K+ depletion during AngII infusion and, thus, prevent NCC accumulation. A2K fed rats exhibited normal plasma [K+] and 2-fold higher K+ excretion and plasma [aldosterone] versus A1K. In A1K rats, NCC, NCCpS71, and NCCpT53 abundance increased 1.5- to 3-fold versus controls (p< 0.05). The rise in NCC and NCCp abundance was prevented in the A2K rats, yet blood pressure did not significantly decrease. ENaC subunit abundance and cleavage increased 1.5- to 3-fold in both A1K and A2K; ROMK abundance was unaffected by Ang II or dietary K+. In summary, the accumulation and phosphorylation of NCC seen during chronic AngII infusion hypertension is likely secondary to potassium deficiency driven by ENaC stimulation.

CD8+ T cells stimulate Na-Cl co-transporter NCC in distal convoluted tubules leading to salt-sensitive hypertension

“…Recent reports from Terker et al 27. and Veiras et al 28. indicated that plasma potassium plays an important role in regulating NCC in DCTs, with Kir4.1 possibly involved27.…”

“…Although direct evidence of ClC-K regulating NCC is missing, patients carrying ClC-K mutations demonstrate Gitelman's syndrome2526 leading us to speculate that the NCC in DCT segments is affected by the function of ClC-K. Recent studies suggest that changes in plasma K + concentration and the basolateral K + channel Kir4.1, a known downstream target of Src kinases, may play important roles in regulating ClC-K, consequently affecting NCC expression and activation27282930. However, direct evidence linking the regulation of Kir4.1 and the pathogenesis of salt-sensitive hypertension is missing.…”

Collecting Duct Nitric Oxide Synthase 1ß Activation Maintains Sodium Homeostasis During High Sodium Intake Through Suppression of Aldosterone and Renal Angiotensin II Pathways

“…Immunoreactivity was visualized using fluorescently tagged secondary antibodies (0.1 ng/mL) and the LI‐COR infrared Odyssey Imaging System. Antibodies used in this study can be found in Table and have been previously validated . To ensure equal loading of all samples, Western blots for actin and Coomassie Blue staining of each membrane were performed.…”

Essential role of Kir5.1 channels in renal salt handling and blood pressure control

“…The beneficial effects of dietary potassium are most likely related to the reduced activity of NKCC2 and NCC. It was recently reported that NCC activity in the DCT is induced by augmented plasma K + (41,50). The rapid phosphorylation of NCC in response to a low-potassium diet involves activation of WNK/SPAK by decreased intracellular Cl -concentrations due to hyperpolarization of the cell membrane in the DCT cells (8,51).…”