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Record W2790900135 · doi:10.1371/journal.pone.0193032

Endothelial mineralocorticoid receptor ablation does not alter blood pressure, kidney function or renal vessel contractility

2018· article· en· W2790900135 on OpenAlexfundno aff
Sidsel B. Laursen, Stine H. Finsen, Niels Marcussen, Susan E. Quaggin, Pernille Hansen, Henrik Dimke

Bibliographic record

VenuePLoS ONE · 2018
Typearticle
Languageen
FieldMedicine
TopicHormonal Regulation and Hypertension
Canadian institutionsnot available
FundersNational Eye InstituteFonden til Lægevidenskabens FremmeH. Lundbeck A/SUniversity of California, San FranciscoNovo Nordisk FondenCanadian Institutes of Health ResearchA.P. Møller og Hustru Chastine Mc-Kinney Møllers Fond til almene FormaalDanmarks Frie ForskningsfondNovo NordiskHjerteforeningenSyddansk UniversitetLundbeckfondenCarlsbergfondetDeutsches KrebsforschungszentrumSundhed og Sygdom, Det Frie ForskningsrådE-Rare
KeywordsEndocrinologyInternal medicineAldosteroneKidneyMineralocorticoid receptorRenal functionMineralocorticoidAfferent arteriolesBlood pressureRenin–angiotensin systemMedicineExcretionRenal blood flowUrinary systemVasoconstriction

Abstract

fetched live from OpenAlex

Aldosterone blockade confers substantial cardiovascular and renal protection. The effects of aldosterone on mineralocorticoid receptors (MR) expressed in endothelial cells (EC) within the renal vasculature have not been delineated. We hypothesized that lack of MR in EC may be protective in renal vasculature and examined this by ablating the Nr3c2 gene in endothelial cells (EC-MR) in mice. Blood pressure, heart rate and PAH clearance were measured using indwelling catheters in conscious mice. The role of the MR in EC on contraction and relaxation was investigated in the renal artery and in perfused afferent arterioles. Urinary sodium excretion was determined by use of metabolic cages. EC-MR transgenics had markedly decreased MR expression in isolated aortic endothelial cells as compared to littermates (WT). Blood pressure and effective renal plasma flow at baseline and following AngII infusion was similar between groups. No differences in contraction and relaxation were observed between WT and EC-MR KO in isolated renal arteries during baseline or following 2 or 4 weeks of AngII infusion. The constriction or dilatations of afferent arterioles between genotypes were not different. No changes were found between the groups with respect to urinary excretion of sodium after 4 weeks of AngII infusion, or in urinary albumin excretion and kidney morphology. In conclusion, deletion of the EC-MR does not confer protection towards the development of hypertension, endothelial dysfunction of renal arteries or renal function following prolonged AngII-infusion.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.001
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesInsufficient payload (model declined to judge)
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.082
Threshold uncertainty score0.998

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.001
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0030.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.043
GPT teacher head0.254
Teacher spread0.211 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

Study designBench or experimental
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations19
Published2018
Admission routes1
Has abstractyes

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Same venuePLoS ONESame topicHormonal Regulation and HypertensionFrench-language works237,207