ArticlePflugers Archiv : European journal of physiology2012
Aldosterone does not require angiotensin II to activate NCC through a WNK4-SPAK-dependent pathway.
Article in Pflugers Archiv : European journal of physiology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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Who cites it
49 citing papers in PubMed.
- Aldosterone: From Essential Tubular Regulator to Pathological Driver-Physiology, Disease, and Therapeutic Advances.International journal of molecular sciences · 2025Review
- SECS, drugs, and Rac1&Rho: regulation of EnNaC in vascular endothelial cells.Pflugers Archiv : European journal of physiology · 2025Article
- Sodium Chloride Cotransporter in Hypertension.Biomedicines · 2024Review
- Navigating the multifaceted intricacies of the NaPhysiological reviews · 2024Review
- Monogenic Hypertension Linked to the Renin-Angiotensin-Aldosterone System.Anatolian journal of cardiology · 2024Article
- Update on NKCC2 regulation in the thick ascending limb (TAL) by membrane trafficking, phosphorylation, and protein-protein interactions.Frontiers in physiology · 2024Review
- Article
- Molecular mechanisms for the modulation of blood pressure and potassium homeostasis by the distal convoluted tubule.EMBO molecular medicine · 2022Review
- Potassium Effects on NCC Are Attenuated during Inhibition of Cullin E3-Ubiquitin Ligases.Cells · 2021Article
- Mechanisms coupling sodium and magnesium reabsorption in the distal convoluted tubule of the kidney.Acta physiologica (Oxford, England) · 2021Review
- Glucocorticoid receptor activation stimulates the sodium-chloride cotransporter and influences the diurnal rhythm of its phosphorylation.American journal of physiology. Renal physiology · 2019Article
- Modified HEK cells simulate DCT cells in their sensitivity and response to changes in extracellular K.Physiological reports · 2019Article
- Phthalate-associated hypertension in premature infants: a prospective mechanistic cohort study.Pediatric nephrology (Berlin, Germany) · 2019Observational
- Rapid Aldosterone-Mediated Signaling in the DCT Increases Activity of the Thiazide-Sensitive NaCl Cotransporter.Journal of the American Society of Nephrology : JASN · 2019Article
- The interplay of renal potassium and sodium handling in blood pressure regulation: critical role of the WNK-SPAK-NCC pathway.Journal of human hypertension · 2019Review
- Novel zebrafish behavioral assay to identify modifiers of the rapid, nongenomic stress response.Genes, brain, and behavior · 2019Article
- Na restriction activates epithelial Na channels in rat kidney through two mechanisms and decreases distal NaThe Journal of physiology · 2018Article
- The thiazide sensitive sodium chloride co-transporter NCC is modulated by site-specific ubiquitylation.Scientific reports · 2017Article
- Responses of distal nephron NaAmerican journal of physiology. Renal physiology · 2017Article
- In Primary Aldosteronism, Mineralocorticoids Influence Exosomal Sodium-Chloride Cotransporter Abundance.Journal of the American Society of Nephrology : JASN · 2017Article
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10 authors.
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Abstract
We and others have recently shown that angiotensin II can activate the sodium chloride cotransporter (NCC) through a WNK4-SPAK-dependent pathway. Because WNK4 was previously shown to be a negative regulator of NCC, it has been postulated that angiotensin II converts WNK4 to a positive regulator. Here, we ask whether aldosterone requires angiotensin II to activate NCC and if their effects are additive. To do so, we infused vehicle or aldosterone in adrenalectomized rats that also received the angiotensin receptor blocker losartan. In the presence of losartan, aldosterone was still capable of increasing total and phosphorylated NCC twofold to threefold. The kinases WNK4 and SPAK also increased with aldosterone and losartan. A dose-dependent relationship between aldosterone and NCC, SPAK, and WNK4 was identified, suggesting that these are aldosterone-sensitive proteins. As more functional evidence of increased NCC activity, we showed that rats receiving aldosterone and losartan had a significantly greater natriuretic response to hydrochlorothiazide than rats receiving losartan only. To study whether angiotensin II could have an additive effect, rats receiving aldosterone with losartan were compared with rats receiving aldosterone only. Rats receiving aldosterone only retained more sodium and had twofold to fourfold increase in phosphorylated NCC. Together, our results demonstrate that aldosterone does not require angiotensin II to activate NCC and that WNK4 appears to act as a positive regulator in this pathway. The additive effect of angiotensin II may favor electroneutral sodium reabsorption during hypovolemia and may contribute to hypertension in diseases with an activated renin-angiotensin-aldosterone system.
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