Journal article
Na+-sensitive elevation in blood pressure is ENaC independent in diet-induced obesity and insulin resistance
American journal of physiology. Renal physiology, Vol.310(9), pp.F812-F820
05/01/2016
DOI: 10.1152/ajprenal.00265.2015
PMCID: PMC4867314
PMID: 26841823
Abstract
The majority of patients with obesity, insulin resistance, and metabolic syndrome have hypertension, but the mechanisms of hypertension are poorly understood. In these patients, impaired sodium excretion is critical for the genesis of Na(+)-sensitive hypertension, and prior studies have proposed a role for the epithelial Na(+) channel (ENaC) in this syndrome. We characterized high fat-fed mice as a model in which to study the contribution of ENaC-mediated Na(+) reabsorption in obesity and insulin resistance. High fat-fed mice demonstrated impaired Na(+) excretion and elevated blood pressure, which was significantly higher on a high-Na(+) diet compared with low fat-fed control mice. However, high fat-fed mice had no increase in ENaC activity as measured by Na(+) transport across microperfused cortical collecting ducts, electrolyte excretion, or blood pressure. In addition, we found no difference in endogenous urinary aldosterone excretion between groups on a normal or high-Na(+) diet. High fat-fed mice provide a model of metabolic syndrome, recapitulating obesity, insulin resistance, impaired natriuresis, and a Na(+)-sensitive elevation in blood pressure. Surprisingly, in contrast to previous studies, our data demonstrate that high fat feeding of mice impairs natriuresis and produces elevated blood pressure that is independent of ENaC activity and likely caused by increased Na(+) reabsorption upstream of the aldosterone-sensitive distal nephron.
Details
- Title: Subtitle
- Na+-sensitive elevation in blood pressure is ENaC independent in diet-induced obesity and insulin resistance
- Creators
- Jonathan M Nizar - Stanford UniversityWuxing Dong - Stanford UniversityRobert B McClellan - Stanford UniversityMariana Labarca - Stanford UniversityYuehan Zhou - Icahn School of Medicine at Mount SinaiJared Wong - Stanford UniversityDonald G Goens - Stanford UniversityMingming Zhao - Stanford UniversityNona Velarde - Stanford UniversityDaniel Bernstein - Stanford UniversityMichael Pellizzon - Banyan BiomarkersLisa M Satlin - Icahn School of Medicine at Mount SinaiVivek Bhalla - Stanford University
- Resource Type
- Journal article
- Publication Details
- American journal of physiology. Renal physiology, Vol.310(9), pp.F812-F820
- DOI
- 10.1152/ajprenal.00265.2015
- PMID
- 26841823
- PMCID
- PMC4867314
- ISSN
- 0363-6127
- eISSN
- 1522-1466
- Grant note
- P30 DK079307 / NIDDK NIH HHS R01 DK091565 / NIDDK NIH HHS R03 DK083613 / NIDDK NIH HHS R01 DK038470 / NIDDK NIH HHS UL1 TR001085 / NCATS NIH HHS
- Language
- English
- Date published
- 05/01/2016
- Academic Unit
- Nephrology; Internal Medicine
- Record Identifier
- 9984359928402771
Metrics
8 Record Views