Eicosanoid-Regulated Myeloid ENaC and Isolevuglandin Formation in Human Salt-Sensitive Hypertension.
antigen-presenting cells
cytochromes
epithelial sodium channel
hypertension
isolevuglandin
Journal
Hypertension (Dallas, Tex. : 1979)
ISSN: 1524-4563
Titre abrégé: Hypertension
Pays: United States
ID NLM: 7906255
Informations de publication
Date de publication:
07 Sep 2023
07 Sep 2023
Historique:
medline:
7
9
2023
pubmed:
7
9
2023
entrez:
7
9
2023
Statut:
aheadofprint
Résumé
The mechanisms by which salt increases blood pressure in people with salt sensitivity remain unclear. Our previous studies found that high sodium enters antigen-presenting cells (APCs) via the epithelial sodium channel and leads to the production of isolevuglandins and hypertension. In the current mechanistic clinical study, we hypothesized that epithelial sodium channel-dependent isolevuglandin-adduct formation in APCs is regulated by epoxyeicosatrienoic acids (EETs) and leads to salt-sensitive hypertension in humans. Salt sensitivity was assessed in 19 hypertensive subjects using an inpatient salt loading and depletion protocol. Isolevuglandin-adduct accumulation in APCs was analyzed using flow cytometry. Gene expression in APCs was analyzed using cellular indexing of transcriptomes and epitopes by sequencing analysis of blood mononuclear cells. Plasma and urine EETs were measured using liquid chromatography-mass spectrometry. Baseline isolevuglandin Isolevuglandin formation in APCs responds to acute changes in salt intake in salt-sensitive but not salt-resistant people with hypertension, and this may be regulated by renal EET 14-15. Baseline levels of isolevuglandin
Sections du résumé
BACKGROUND
BACKGROUND
The mechanisms by which salt increases blood pressure in people with salt sensitivity remain unclear. Our previous studies found that high sodium enters antigen-presenting cells (APCs) via the epithelial sodium channel and leads to the production of isolevuglandins and hypertension. In the current mechanistic clinical study, we hypothesized that epithelial sodium channel-dependent isolevuglandin-adduct formation in APCs is regulated by epoxyeicosatrienoic acids (EETs) and leads to salt-sensitive hypertension in humans.
METHODS
METHODS
Salt sensitivity was assessed in 19 hypertensive subjects using an inpatient salt loading and depletion protocol. Isolevuglandin-adduct accumulation in APCs was analyzed using flow cytometry. Gene expression in APCs was analyzed using cellular indexing of transcriptomes and epitopes by sequencing analysis of blood mononuclear cells. Plasma and urine EETs were measured using liquid chromatography-mass spectrometry.
RESULTS
RESULTS
Baseline isolevuglandin
CONCLUSIONS
CONCLUSIONS
Isolevuglandin formation in APCs responds to acute changes in salt intake in salt-sensitive but not salt-resistant people with hypertension, and this may be regulated by renal EET 14-15. Baseline levels of isolevuglandin
Identifiants
pubmed: 37675576
doi: 10.1161/HYPERTENSIONAHA.123.21285
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM