In 2011 Fujita and coworkers proposed that beta-adrenergic stimulation causes decreased serine/threonine-protein kinase WNK4 transcription leading to the activation of Na-Cl cotransporter (NCC) which participates in salt sensitivity and salt hypertension development in rodents.
Potassium has recently been identified as an important driver of NCC activity, and low serum potassium may also contribute to increased renal sodium reabsorption and hypertension in CS.
These findings suggest that NCC-mediated Cl<sup>-</sup> uptake plays important roles in the development of aldosterone-induced hypertension and renal injury.
The SLC12A3-Arg913Gln variation may be associated with increased blood pressure and UAER and, therefore, could be used to predict the development and progression of DN-ESRD in Chinese T2DM patients undergoing hemodialysis.
In particular, CD8<sup>+</sup> T cells directly contact the distal convoluted tubule (DCT) in the kidneys of DOCA-salt mice and CD8<sup>+</sup> T cell-injected mice, leading to up-regulation of the Na-Cl co-transporter NCC, p-NCC and the development of salt-sensitive hypertension.
A common pathway between oxidative stress and hypertension induced by CNIs may be identified in the involvement of the activation of RhoA/Rho kinase pathway, key for the induction of hypertension and cardiovascular-renal remodeling, of the oxidative stress mediated increased nitric oxide (NO) metabolism and increased renal sodium retention via increased activity of thiazide-sensitive sodium chloride cotransporter (NCC) in the distal tubule.
These data demonstrate the role of KLHL3 in low-K<sup>+</sup>-mediated induction of NCC; this physiologic adaptation reduces distal electrogenic Na<sup>+</sup> reabsorption, preventing further renal K<sup>+</sup> loss but promoting increased blood pressure.
The present analysis also raises questions about whether mutation-dependent increases in renal tubular activity of ENaC or NCC are even necessary to account for increased risk for salt-dependent hypertension in most patients with such mutations.
Taken together, our findings demonstrate a predominant role played by SLC12A3 gene rs5804 in determining hypertension risk among northeastern Han Chinese.
The pathophysiological significance of this network is illustrated by the fact that modification of each individual protein in the network changes NCC activity and results in salt-dependent hypotension or hypertension.
FHHt (familial hyperkalaemic hypertension; also known as Gordon's syndrome) is a salt-dependent form of hypertension caused by mutations in the regulators of the thiazide-sensitive Na+-Cl- co-transporter NCC [also known as SLC12A3 (solute carrier family 12 member 3)] and is effectively treated by thiazide diuretics and/or dietary salt restriction.
Taken together, these results demonstrate that loss of NEDD4-2 in adult renal tubules causes a new form of mild, salt-sensitive hypertension without hyperkalemia that is characterized by upregulation of NCC, elevation of β/γENaC, but not αENaC, and a normal Na+/K+ balance maintained by downregulation of ENaC activity and upregulation of ROMK.
Here we tested whether STK39, OXSR1, and SLC12A3 genetically contribute to hypertension in the Han Chinese population and how the SNP to SNP or SNP to other risk factors interacts in the pathogenesis of hypertension.
The aim of this review is to provide an overview of the recent developments in the regulation of NCC, highlighting a potential new therapeutic target for the treatment of hypertension.
Lack of association of variants of the renal salt reabsorption-related genes SLC12A3 and ClC-Kb and hypertension in Mongolian and Han populations in Inner Mongolia.
Loss of physiological regulation of the renal thiazide-sensitive Na+-Cl- cotransporter (NCC) by mutant WNK1 or WNK4 results in pseudohypoaldosteronism type II (PHAII) characterized by arterial hypertension and hyperkalemia.