Evidence map›Paper›PMID 24799612›Full record

ArticleHypertension (Dallas, Tex. : 1979)2014

Sympathetic stimulation of thiazide-sensitive sodium chloride cotransport in the generation of salt-sensitive hypertension.

Andrew S Terker, Chao-Ling Yang, James A McCormick, Nicholas P Meermeier, Shaunessy L Rogers, Solveig Grossmann, Katja Trompf, Eric Delpire, Johannes Loffing, David H Ellison

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Hypertension (Dallas, Tex. : 1979), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.

0numbers the graph read from it
0cells of the map it votes in
49citing papers in PubMed
4.3field-weighted citation impact, top 5% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

49 citing papers in PubMed, 78 citations in OpenAlex.

  1. Review
  2. Article
  3. Review
  4. Review
  5. Article
  6. Review
  7. Review
  8. Review
  9. Article
  10. Thirty years of the NaCl cotransporter: from cloning to physiology and structure.American journal of physiology. Renal physiology · 2023
    Review
  11. Review
  12. Inwardly rectifying KAmerican journal of physiology. Cell physiology · 2022
    Review
  13. Landscape of GPCR expression along the mouse nephron.American journal of physiology. Renal physiology · 2021
    Article
  14. Roles of WNK4 and SPAK in KAmerican journal of physiology. Renal physiology · 2021
    Article
  15. Review
  16. Review
  17. WNK4 kinase: from structure to physiology.American journal of physiology. Renal physiology · 2021
    Review
  18. Article
  19. Article
  20. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 2 institutions in 2 countries.

Andrew S TerkerFrom the Division of Nephrology and Hypertension, Department of Medicine, Oregon Health and Science University, Portland (A.S.T., C.-L.Y., J.A.M., N.P.M., S.L.R., D.H.E.); Renal Section, VA Medical Center, Portland, OR (C.-L.Y., N.P.M., D.H.E.); Institute of Anatomy, University of Zurich, Zurich, Switzerland (S.G., K.T., J.L.); and Department of Anesthesiology, Vanderbilt University Medical School, Nashville, TN (E.D.).
Chao-Ling YangFrom the Division of Nephrology and Hypertension, Department of Medicine, Oregon Health and Science University, Portland (A.S.T., C.-L.Y., J.A.M., N.P.M., S.L.R., D.H.E.); Renal Section, VA Medical Center, Portland, OR (C.-L.Y., N.P.M., D.H.E.); Institute of Anatomy, University of Zurich, Zurich, Switzerland (S.G., K.T., J.L.); and Department of Anesthesiology, Vanderbilt University Medical School, Nashville, TN (E.D.).
James A McCormickFrom the Division of Nephrology and Hypertension, Department of Medicine, Oregon Health and Science University, Portland (A.S.T., C.-L.Y., J.A.M., N.P.M., S.L.R., D.H.E.); Renal Section, VA Medical Center, Portland, OR (C.-L.Y., N.P.M., D.H.E.); Institute of Anatomy, University of Zurich, Zurich, Switzerland (S.G., K.T., J.L.); and Department of Anesthesiology, Vanderbilt University Medical School, Nashville, TN (E.D.).
Nicholas P MeermeierFrom the Division of Nephrology and Hypertension, Department of Medicine, Oregon Health and Science University, Portland (A.S.T., C.-L.Y., J.A.M., N.P.M., S.L.R., D.H.E.); Renal Section, VA Medical Center, Portland, OR (C.-L.Y., N.P.M., D.H.E.); Institute of Anatomy, University of Zurich, Zurich, Switzerland (S.G., K.T., J.L.); and Department of Anesthesiology, Vanderbilt University Medical School, Nashville, TN (E.D.).
Shaunessy L RogersFrom the Division of Nephrology and Hypertension, Department of Medicine, Oregon Health and Science University, Portland (A.S.T., C.-L.Y., J.A.M., N.P.M., S.L.R., D.H.E.); Renal Section, VA Medical Center, Portland, OR (C.-L.Y., N.P.M., D.H.E.); Institute of Anatomy, University of Zurich, Zurich, Switzerland (S.G., K.T., J.L.); and Department of Anesthesiology, Vanderbilt University Medical School, Nashville, TN (E.D.).
Solveig GrossmannFrom the Division of Nephrology and Hypertension, Department of Medicine, Oregon Health and Science University, Portland (A.S.T., C.-L.Y., J.A.M., N.P.M., S.L.R., D.H.E.); Renal Section, VA Medical Center, Portland, OR (C.-L.Y., N.P.M., D.H.E.); Institute of Anatomy, University of Zurich, Zurich, Switzerland (S.G., K.T., J.L.); and Department of Anesthesiology, Vanderbilt University Medical School, Nashville, TN (E.D.).
Katja TrompfFrom the Division of Nephrology and Hypertension, Department of Medicine, Oregon Health and Science University, Portland (A.S.T., C.-L.Y., J.A.M., N.P.M., S.L.R., D.H.E.); Renal Section, VA Medical Center, Portland, OR (C.-L.Y., N.P.M., D.H.E.); Institute of Anatomy, University of Zurich, Zurich, Switzerland (S.G., K.T., J.L.); and Department of Anesthesiology, Vanderbilt University Medical School, Nashville, TN (E.D.).
Eric DelpireFrom the Division of Nephrology and Hypertension, Department of Medicine, Oregon Health and Science University, Portland (A.S.T., C.-L.Y., J.A.M., N.P.M., S.L.R., D.H.E.); Renal Section, VA Medical Center, Portland, OR (C.-L.Y., N.P.M., D.H.E.); Institute of Anatomy, University of Zurich, Zurich, Switzerland (S.G., K.T., J.L.); and Department of Anesthesiology, Vanderbilt University Medical School, Nashville, TN (E.D.).
Johannes LoffingFrom the Division of Nephrology and Hypertension, Department of Medicine, Oregon Health and Science University, Portland (A.S.T., C.-L.Y., J.A.M., N.P.M., S.L.R., D.H.E.); Renal Section, VA Medical Center, Portland, OR (C.-L.Y., N.P.M., D.H.E.); Institute of Anatomy, University of Zurich, Zurich, Switzerland (S.G., K.T., J.L.); and Department of Anesthesiology, Vanderbilt University Medical School, Nashville, TN (E.D.).
David H EllisonFrom the Division of Nephrology and Hypertension, Department of Medicine, Oregon Health and Science University, Portland (A.S.T., C.-L.Y., J.A.M., N.P.M., S.L.R., D.H.E.); Renal Section, VA Medical Center, Portland, OR (C.-L.Y., N.P.M., D.H.E.); Institute of Anatomy, University of Zurich, Zurich, Switzerland (S.G., K.T., J.L.); and Department of Anesthesiology, Vanderbilt University Medical School, Nashville, TN (E.D.). ellisond@ohsu.edu.
Portland VA Medical Center · USUniversity of Zurich · CH

Funding

WNK-SPAK signaling in the Distal NephronR01DK093501 · NIDDK · VANDERBILT UNIVERSITY MEDICAL CENTER · PI Eric J Delpire, Paul A Welling · 2012 to 2026
$12.1M
WNK Kinase Regulation of Thiazide-sensitive NaCl TransportR01DK051496 · NIDDK · UNIVERSITY OF COLORADO DENVER · PI David Hoadley Ellison, CHAO-LING YANG · 1998 to 2026
$8.4M
Regulation of sodium transport and blood pressure by SPAK/OSR1 kinasesR01DK098141 · NIDDK · OREGON HEALTH & SCIENCE UNIVERSITY · PI JAMES A MCCORMICK, Ujwal Shinde · 2014 to 2026
$4.2M
KINASES IN ION COTRANSPORTER FUNCTIONR01GM074771 · NIGMS · VANDERBILT UNIVERSITY MEDICAL CENTER · PI DELPIRE, ERIC J · 2007 to 2014
$2.8M
Nephrology Training GrantT32DK067864 · NIDDK · OREGON HEALTH & SCIENCE UNIVERSITY · PI ELLISON, DAVID H · 2006 to 2015
$1.2M
Deltavision RT Image Restoration System for Established Research Core FacilityS10RR023432 · NCRR · OREGON HEALTH & SCIENCE UNIVERSITY · PI KELLER, THOMAS J · 2007 to 2007
$365k
NCRR NIH HHS S10 RR023432NCRR NIH HHS S10-RR023432NIDDK NIH HHS DK093501NIDDK NIH HHS DK51496NIDDK NIH HHS R01 DK051496NIDDK NIH HHS R01 DK093501NIDDK NIH HHS R01 DK098141NIDDK NIH HHS T32 DK067864NIGMS NIH HHS GM074771NIGMS NIH HHS R01 GM074771
6 · The paper itself

Abstract

Excessive renal efferent sympathetic nerve activity contributes to hypertension in many circumstances. Although both hemodynamic and tubular effects likely participate, most evidence supports a major role for α-adrenergic receptors in mediating the direct epithelial stimulation of sodium retention. Recently, it was reported, however, that norepinephrine activates the thiazide-sensitive NaCl cotransporter (NCC) by stimulating β-adrenergic receptors. Here, we confirmed this effect and developed an acute adrenergic stimulation model to study the signaling cascade. The results show that norepinephrine increases the abundance of phosphorylated NCC rapidly (161% increase), an effect largely dependent on β-adrenergic receptors. This effect is not mediated by the activation of angiotensin II receptors. We used immunodissected mouse distal convoluted tubule to show that distal convoluted tubule cells are especially enriched for β₁-adrenergic receptors, and that the effects of adrenergic stimulation can occur ex vivo (79% increase), suggesting they are direct. Because the 2 protein kinases, STE20p-related proline- and alanine-rich kinase (encoded by STK39) and oxidative stress-response kinase 1, phosphorylate and activate NCC, we examined their roles in norepinephrine effects. Surprisingly, norepinephrine did not affect STE20p-related proline- and alanine-rich kinase abundance or its localization in the distal convoluted tubule; instead, we observed a striking activation of oxidative stress-response kinase 1. We confirmed that STE20p-related proline- and alanine-rich kinase is not required for NCC activation, using STK39 knockout mice. Together, the data provide strong support for a signaling system involving β₁-receptors in the distal convoluted tubule that activates NCC, at least in part via oxidative stress-response kinase 1. The results have implications about device- and drug-based treatment of hypertension.

Indexed as

AnimalsBlood PressureHypertensionKidney Tubules, DistalMiceNorepinephrinePhosphorylationReceptors, Adrenergic, beta-1Sodium Chloride, DietarySolute Carrier Family 12, Member 3Sympathetic Nervous SystemNorepinephrineReceptors, Adrenergic, beta-1Sodium Chloride, DietarySolute Carrier Family 12, Member 3diureticshypertensionion transportsodium-potassium-chloride symporterssympathetic nervous system

Identifiers

PMID24799612
PMCPMC4061471
OpenAlexW2104001407

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

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.