Tempol Alters Urinary Extracellular Vesicle Lipid Content and Release While Reducing Blood Pressure during the Development of Salt-Sensitive Hypertension

Salt-sensitive hypertension resulting from an increase in blood pressure after high dietary salt intake is associated with an increase in the production of reactive oxygen species (ROS). ROS are known to increase the activity of the epithelial sodium channel (ENaC), and therefore, they have an indir...

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Main Authors: Kevin M. Chacko, Mohammad-Zaman Nouri, Whitney C. Schramm, Zeeshan Malik, Lauren P. Liu, Nancy D. Denslow, Abdel A. Alli
Format: Article
Language:English
Published: MDPI AG 2021-12-01
Series:Biomolecules
Subjects:
Online Access:https://www.mdpi.com/2218-273X/11/12/1804
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author Kevin M. Chacko
Mohammad-Zaman Nouri
Whitney C. Schramm
Zeeshan Malik
Lauren P. Liu
Nancy D. Denslow
Abdel A. Alli
author_facet Kevin M. Chacko
Mohammad-Zaman Nouri
Whitney C. Schramm
Zeeshan Malik
Lauren P. Liu
Nancy D. Denslow
Abdel A. Alli
author_sort Kevin M. Chacko
collection DOAJ
description Salt-sensitive hypertension resulting from an increase in blood pressure after high dietary salt intake is associated with an increase in the production of reactive oxygen species (ROS). ROS are known to increase the activity of the epithelial sodium channel (ENaC), and therefore, they have an indirect effect on sodium retention and increasing blood pressure. Extracellular vesicles (EVs) carry various molecules including proteins, microRNAs, and lipids and play a role in intercellular communication and intracellular signaling in health and disease. We investigated changes in EV lipids, urinary electrolytes, osmolality, blood pressure, and expression of renal ENaC and its adaptor protein, MARCKS/MARCKS Like Protein 1 (MLP1) after administration of the antioxidant Tempol in salt-sensitive hypertensive 129Sv mice. Our results show Tempol infusion reduces systolic blood pressure and protein expression of the alpha subunit of ENaC and MARCKS in the kidney cortex of hypertensive 129Sv mice. Our lipidomic data show an enrichment of diacylglycerols and monoacylglycerols and reduction in ceramides, dihydroceramides, and triacylglycerols in urinary EVs from these mice after Tempol treatment. These data will provide insight into our understanding of mechanisms involving strategies aimed to inhibit ROS to alleviate salt-sensitive hypertension.
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spelling doaj.art-2d0234273fba485c94928cac3f54d5122023-11-23T03:59:25ZengMDPI AGBiomolecules2218-273X2021-12-011112180410.3390/biom11121804Tempol Alters Urinary Extracellular Vesicle Lipid Content and Release While Reducing Blood Pressure during the Development of Salt-Sensitive HypertensionKevin M. Chacko0Mohammad-Zaman Nouri1Whitney C. Schramm2Zeeshan Malik3Lauren P. Liu4Nancy D. Denslow5Abdel A. Alli6Department of Physiology and Functional Genomics, University of Florida, Gainesville, FL 32610, USADepartment of Physiological Sciences and Center for Environmental and Human Toxicology, University of Florida, Gainesville, FL 32610, USADepartment of Physiology and Functional Genomics, University of Florida, Gainesville, FL 32610, USADepartment of Physiology and Functional Genomics, University of Florida, Gainesville, FL 32610, USADepartment of Physiology and Functional Genomics, University of Florida, Gainesville, FL 32610, USADepartment of Physiological Sciences and Center for Environmental and Human Toxicology, University of Florida, Gainesville, FL 32610, USADepartment of Physiology and Functional Genomics, University of Florida, Gainesville, FL 32610, USASalt-sensitive hypertension resulting from an increase in blood pressure after high dietary salt intake is associated with an increase in the production of reactive oxygen species (ROS). ROS are known to increase the activity of the epithelial sodium channel (ENaC), and therefore, they have an indirect effect on sodium retention and increasing blood pressure. Extracellular vesicles (EVs) carry various molecules including proteins, microRNAs, and lipids and play a role in intercellular communication and intracellular signaling in health and disease. We investigated changes in EV lipids, urinary electrolytes, osmolality, blood pressure, and expression of renal ENaC and its adaptor protein, MARCKS/MARCKS Like Protein 1 (MLP1) after administration of the antioxidant Tempol in salt-sensitive hypertensive 129Sv mice. Our results show Tempol infusion reduces systolic blood pressure and protein expression of the alpha subunit of ENaC and MARCKS in the kidney cortex of hypertensive 129Sv mice. Our lipidomic data show an enrichment of diacylglycerols and monoacylglycerols and reduction in ceramides, dihydroceramides, and triacylglycerols in urinary EVs from these mice after Tempol treatment. These data will provide insight into our understanding of mechanisms involving strategies aimed to inhibit ROS to alleviate salt-sensitive hypertension.https://www.mdpi.com/2218-273X/11/12/1804TempolROSENaCMARCKSsalt-sensitive hypertensionextracellular vesicles
spellingShingle Kevin M. Chacko
Mohammad-Zaman Nouri
Whitney C. Schramm
Zeeshan Malik
Lauren P. Liu
Nancy D. Denslow
Abdel A. Alli
Tempol Alters Urinary Extracellular Vesicle Lipid Content and Release While Reducing Blood Pressure during the Development of Salt-Sensitive Hypertension
Biomolecules
Tempol
ROS
ENaC
MARCKS
salt-sensitive hypertension
extracellular vesicles
title Tempol Alters Urinary Extracellular Vesicle Lipid Content and Release While Reducing Blood Pressure during the Development of Salt-Sensitive Hypertension
title_full Tempol Alters Urinary Extracellular Vesicle Lipid Content and Release While Reducing Blood Pressure during the Development of Salt-Sensitive Hypertension
title_fullStr Tempol Alters Urinary Extracellular Vesicle Lipid Content and Release While Reducing Blood Pressure during the Development of Salt-Sensitive Hypertension
title_full_unstemmed Tempol Alters Urinary Extracellular Vesicle Lipid Content and Release While Reducing Blood Pressure during the Development of Salt-Sensitive Hypertension
title_short Tempol Alters Urinary Extracellular Vesicle Lipid Content and Release While Reducing Blood Pressure during the Development of Salt-Sensitive Hypertension
title_sort tempol alters urinary extracellular vesicle lipid content and release while reducing blood pressure during the development of salt sensitive hypertension
topic Tempol
ROS
ENaC
MARCKS
salt-sensitive hypertension
extracellular vesicles
url https://www.mdpi.com/2218-273X/11/12/1804
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