NCC kidney

PURPOSE OF REVIEW: Hypertension, commonly known as high blood pressure, is a widespread health condition affecting a large number of individuals across the globe. Although lifestyle choices and environmental factors are known to have a significant impact on its development, there is growing recognition of the influence of genetic factors in the pathogenesis of hypertension. This review specifically focuses on the hereditary causes of hypertension that are associated with increased sodium transport through the thiazide-sensitive NaCl cotransporter (NCC) or amiloride-sensitive epithelial sodium channel (ENaC), crucial mechanisms involved in regulating blood pressure in the kidneys...

The WNK4-SPAK/OSR1 pathway mediates activating phosphorylation of the furosemide-sensitive Na+ -K+ -2Cl- cotransporter (NKCC2) and the thiazide-sensitive NaCl cotransporter (NCC). The commonly used pT96/pT101-pNKCC2 antibody cross-reacts with pT53-NCC in mice on the C57BL/6 background due to a five amino acid deletion. We generated a new C57BL/6-specific pNKCC2 antibody (anti-pT96-NKCC2) and tested the hypothesis that the WNK4-SPAK/OSR1 pathway strongly regulates phosphorylation of NCC but not NKCC2. In C57BL/6 mice, anti-pT96-NKCC2 detected pNKCC2 and did not cross-react with NCC...

INTRODUCTION: Nephrotic syndrome (NS) is characterized by renal sodium and water retention. The mechanisms are not fully elucidated. METHODS: The NS rat model was established by single intraperitoneal injection of 100 mg/kg puromycin aminonucleoside (PAN). The plasma electrolyte level and urinary sodium excretion were monitored dynamically. The changes of some sodium transporters, including epithelial Na+ channel (ENaC), Na+ /H+ exchanger 3 (NHE3), Na+ -K+ -2Cl- cotransporter 2 (NKCC2) and Na+ -Cl- cotransporter (NCC) in renal cortex at different time points and the level of peripheral circulation factors were detected...

The serine proteases CAP1/Prss8 and CAP3/St14 are identified as ENaC channel-activating proteases in vitro, highly suggesting that they are required for proteolytic activation of ENaC in vivo. The present study tested whether CAP3/St14 is relevant for renal proteolytic ENaC activation and affects ENaC-mediated Na+ absorption following Na+ deprivation conditions. CAP3/St14 knockout mice exhibit a significant decrease in CAP1/Prss8 protein expression with altered ENaC subunit and decreased pNCC protein abundances but overall maintain sodium balance...

Carbohydrates increase kidney stone risk and increase urine calcium and magnesium. We hypothesize that effects of glucose as an allosteric modulator of calcium-sensing receptor may mediate this effect. Six healthy subjects were on a low sodium diet before consuming 100 grams of glucose beverage. Timed fasting (3) and post-glucose (6) urine and blood samples were collected every 30-minutes. Urine composition and serum markers were measured and microvesicular abundance of tubular transport proteins (NHE3, NKCC2, NCC, and TRPV5) were quantified...

Chronic infusion of subpressor level of Angiotensin II (AngII) increases the abundance of Na+ transporters along the distal nephron, balanced by suppression of Na+ transporters along the proximal tubule and medullary thick ascending limb (defined as proximal nephron), which impacts K+ handling along the entire renal tubule. The objective of this study was to quantitatively assess the impact of chronic AngII on the renal handling of Na+ and K+ in female rats, using a computational model of the female rat renal tubule...

Consumption of low dietary potassium, common with ultra-processed foods, activates the thiazide-sensitive sodium chloride cotransporter (NCC) via the WNK-SPAK kinase pathway to induce salt retention and elevate blood pressure (BP). However, it remains unclear how high potassium "DASH-like" diets inactivate the cotransporter and whether this decreases BP. A transcriptomic screen identified Ppp1C⍺, encoding PP1A, as a potassium up-regulated gene, and its negative regulator, Ppp1r1a, as a potassium-suppressed gene in the kidney...

Transporters of the solute carrier family 12 (SLC12) carry inorganic cations such as Na+ and/or K+ alongside Cl across the plasma membrane of cells. These tightly coupled, electroneutral, transporters are expressed in almost all tissues/organs in the body where they fulfil many critical functions. The family includes two key transporters participating in salt reabsorption in the kidney: the Na-K-2Cl cotransporter-2 (NKCC2), expressed in the loop of Henle, and the Na-Cl cotransporter (NCC), expressed in the distal convoluted tubule...

The primary structure of the thiazide-sensitive NaCl cotransporter (NCC) was resolved 30 years ago by the molecular identification of the cDNA encoding this cotransporter, from the winter's flounder urinary bladder, following a functional expression strategy. This review outlines some aspects of how the knowledge about thiazide diuretics and NCC evolved, the history of the cloning process, and the expansion of the SLC12 family of electroneutral cotransporters. The diseases associated with activation or inactivation of NCC are discussed, as well as the molecular model by which the activity of NCC is regulated...

PURPOSE OF REVIEW: An increasing amount of evidence points out to a role for the thiazide-sensitive Na+:Cl- cotransporter, NCC, in the blood pressure alterations observed in conditions of pathologically high or pathologically low aldosterone. Here, we briefly review this evidence that is changing our perception of the pathophysiology of primary aldosteronism. RECENT FINDINGS: Although initially NCC was thought to be a direct target of aldosterone, more recent evidence suggests that NCC is only indirectly regulated by aldosterone, at least in a chronic setting...

PURPOSE OF REVIEW: Regulation of the sodium chloride cotransporter (NCC) in the distal convoluted tubule (DCT) plays a crucial role in renal salt handling. The calcium-sensing receptor (CaSR) has been shown to activate NCC through the WNK4-SPAK pathway, which is independent of the Renin-Angiotensin-Aldosterone system. In this review, we examine new information about the mechanism of how the CaSR regulates NCC through the WNK4-SPAK pathway and its physiological and therapeutic implications...

BACKGROUND: Studies reported that kelch-like protein 3 (KLHL3)-Cullin3(CUL3) E3 ligase ubiquitinated with-no-lysine kinase 4 (WNK4). Impaired WNK4 ubiquitination plays a key role in Familial hyperkalemic hypertension (FHHt, also called pseudohypoaldosteronism type II) which results from overaction of thiazide-sensitive sodium chloride cotransport (NCC). In addition, researchers have also found that dietary potassium deficiency activates NCC along the renal distal convoluted tubule (DCT)...

BACKGROUND: Noncardiac comorbidities (NCCs) are common in patients with heart failure (HF), but how they jointly affect exercise capacity and functional status is relatively unexplored. OBJECTIVES: This study sought to investigate the cumulative effects of NCC on exercise capacity and functional status in chronic HF. METHODS: Baseline NCC-status was assessed in HF-ACTION (Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training), IRONOUT-HF (Oral Iron Repletion Effects on Oxygen Uptake in Heart Failure), NEAT-HFpEF (Nitrate's Effect on Activity Tolerance in Heart Failure With Preserved Ejection Fraction), INDIE-HFpEF (Inorganic Nitrite Delivery to Improve Exercise Capacity in HFpEF), and RELAX-HFpEF (Phosphodiesterase-5 Inhibition to Improve Clinical Status and Exercise Capacity in Heart Failure with Preserved Ejection Fraction) trials, and relations with peak Vo2 and 6-minute walk test (6MWT), Kansas City Cardiomyopathy Questionnaire (KCCQ), and all-cause death were determined according to HF type (with reduced vs preserved ejection fraction)...

BACKGROUND: The expression of NGAL/lcn2 (neutrophil gelatinase-associated lipocalin) is directly modulated by mineralocorticoid receptor activation but its role in blood pressure control is unclear. METHODS: a potential relationship between NGAL plasma levels, systolic blood pressure and urinary Na excretion was assessed in the STANISLAS cohort. The specific role of NGAL/lcn2 in salt-sensitive hypertension was studied using lcn2-knockout mice (lcn2 KO) fed with low-Na diet (0Na)...

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INTRODUCTION: The putative "renal-K switch" mechanism links dietary potassium intake with sodium retention and involves activation of the sodium chloride (NaCl) cotransporter (NCC) in the distal convoluted tubule in response to low potassium intake, and suppression in response to high potassium intake. This study examined NCC abundance and phosphorylation (phosphorylated NCC [pNCC]) in urinary extracellular vesicles (uEVs) isolated from healthy adults on a high sodium diet to determine tubular responses to alteration in potassium chloride (KCl) intake...

Hypertension is one of the major health problems leading to the development of cardiovascular diseases. Despite a rapid expansion in global hypertension prevalence, molecular mechanisms leading to hypertension are not fully understood largely due to the complexity of pathogenesis involving several factors. Salt intake is recognized as a leading determinant of blood pressure, since reduced dietary salt intake is related to lower morbidity and mortality, and hypertension in relation to cardiovascular events. Compared with salt-resistant populations, salt-sensitive individuals exhibit high sensitivity in blood pressure responses according to changes in salt intake...

AIMS: To evaluate the prevalence and associations of non-cardiac comorbidities (NCCs) with in-hospital and post-discharge outcomes in acute heart failure (AHF) across the ejection fraction (EF) spectrum. METHODS AND RESULTS: The 9326 AHF patients from European Society of Cardiology (ESC)-Heart Failure Association (HFA)-EURObservational Research Programme Heart Failure Long-Term Registry had complete information for the following 12 NCCs: anaemia, chronic obstructive pulmonary disease (COPD), diabetes, depression, hepatic dysfunction, renal dysfunction, malignancy, Parkinson's disease, peripheral vascular disease (PVD), rheumatoid arthritis, sleep apnoea, and stroke/transient ischaemic attack (TIA)...

Virtually all of the dietary potassium intake is absorbed in the intestine, over 90% of which is excreted by the kidneys regarded as the most important organ of potassium excretion in the body. The renal excretion of potassium results primarily from the secretion of potassium by the principal cells in the aldosterone-sensitive distal nephron (ASDN), which is coupled to the reabsorption of Na+ by the epithelial Na+ channel (ENaC) located at the apical membrane of principal cells. When Na+ is transferred from the lumen into the cell by ENaC, the negativity in the lumen is relatively increased...

The kidney plays a central role in maintaining the fluid and electrolyte homeostasis in the body. Bicarbonate transporters NBCn1, NBCn2, and AE2 are expressed at the basolateral membrane of the medullary thick ascending limb (mTAL). In a previous study, NBCn1, NBCn2, and AE2 are proposed to play as a regulatory pathway to decrease NaCl reabsorption in the mTAL under high salt condition. When heterologously expressed, the activity of these transporters could be stimulated by the InsP3R binding protein released with inositol 1,4,5-trisphosphate (IRBIT), L-IRBIT (collectively the IRBITs), or protein phosphatase PP1...