ArticlePflugers Archiv : European journal of physiology2011
NKCC2 is activated in Milan hypertensive rats contributing to the maintenance of salt-sensitive hypertension.
Article in Pflugers Archiv : European journal of physiology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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17 citing papers in PubMed, 30 citations in OpenAlex.
- Tandem Upregulation of Ion Transporters in Thick Ascending Limb of Henle's Loop of Young Milan Hypertensive Strain of Rats.Kidney & blood pressure research · 2025Article
- Role of ENaC in gender-associated differences in blood pressure.Iranian journal of basic medical sciences · 2025Article
- Update on NKCC2 regulation in the thick ascending limb (TAL) by membrane trafficking, phosphorylation, and protein-protein interactions.Frontiers in physiology · 2024Review
- Interactions between diabetic and hypertensive drugs: a pharmacogenetics approach.Molecular genetics and genomics : MGG · 2023Review
- Kidney and blood pressure regulation-latest evidence for molecular mechanisms.Clinical kidney journal · 2023Review
- Ubiquitination of NKCC2 by the cullin-RING E3 ubiquitin ligase family in the thick ascending limb of the loop of Henle.American journal of physiology. Renal physiology · 2023Article
- Role of PKC in the Regulation of the Human Kidney Chloride Channel ClC-Ka.Scientific reports · 2020Article
- NHA2 promotes cyst development in an in vitro model of polycystic kidney disease.The Journal of physiology · 2019Article
- Thick Ascending Limb Sodium Transport in the Pathogenesis of Hypertension.Physiological reviews · 2019Review
- Activation of Renal (Pro)Renin Receptor Contributes to High Fructose-Induced Salt Sensitivity.Hypertension (Dallas, Tex. : 1979) · 2017Article
- Azilsartan Improves Salt Sensitivity by Modulating the Proximal Tubular Na+-H+ Exchanger-3 in Mice.PloS one · 2016Article
- Physiology and pathophysiology of SLC12A1/2 transporters.Pflugers Archiv : European journal of physiology · 2014Review
- How the kidney is impacted by the perinatal maternal environment to develop hypertension.Biology of reproduction · 2013Review
- Article
- Molecular physiology of SPAK and OSR1: two Ste20-related protein kinases regulating ion transport.Physiological reviews · 2012Review
- Article
- Salt sensitivity and its implication in clinical practice.Indian heart journalReview
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The Milan hypertensive strain of rats (MHS) develops hypertension as a consequence of the increased tubular Na(+) reabsorption sustained by enhanced expression and activity of the renal tubular Na-K-ATPase. To verify whether the Na-K-2Cl cotransporter (NKCC2) is involved in the maintenance of hypertension in MHS rats, we have analysed the phosphorylation state and the activation of NKCC2 in Milan rats. Western blotting and immunofluorescence experiments were performed using specific antibodies against the regulatory phospho-threonines in the NKCC2 N terminus (R5 antibody). The phosphorylation levels of NKCC2 were significantly increased in the kidney of MHS rats. Moreover, the administration of furosemide in vivo decreased the blood pressure and increased the urine output and natriuresis in MHS rats demonstrating the actual involvement of NKCC2 activity in the pathogenesis of hypertension in this strain of rats. The up-regulation of NKCC2 activity is most probably mediated by a STE20/SPS1-related proline/alanine-rich kinase (SPAK) phosphorylation at serine-325 since it was significantly increased in MHS rats. Interestingly, aldosterone treatment caused an increase in NKCC2 phosphorylation in NKCC2-expressing MDCK cells. In conclusion, we demonstrated an increase in the activity of NKCC2 along the TAL that significantly contributes to the increase in systemic blood pressure in MHS rats. The elevated plasma levels of aldosterone, found in MHS rats, may influence Na(+) balance through a SPAK-dependent regulation of NKCC2 accounting for the maintenance of the hypertensive state in MHS rats.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.