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

• Published in: Biomolecules (Basel, Switzerland) Switzerland), 2021-12, Vol.11 (12), p.1804
• Main Authors: Chacko, Kevin M, Nouri, Mohammad-Zaman, Schramm, Whitney C, Malik, Zeeshan, Liu, Lauren P, Denslow, Nancy D, Alli, Abdel A
• Format: Article
• Language: English
• Subjects: Adaptor proteins; Animals; Antibodies; Antioxidants; Antioxidants - administration & dosage; Antioxidants - pharmacology; Blood pressure; Calmodulin-Binding Proteins - metabolism; Cyclic N-Oxides - administration & dosage; Cyclic N-Oxides - pharmacology; Dietary intake; Disease Models, Animal; Electrolytes; ENaC; Epithelial Sodium Channels - metabolism; Extracellular vesicles; Extracellular Vesicles - chemistry; Extracellular Vesicles - drug effects; Gene Expression Regulation - drug effects; Hypertension; Hypertension - chemically induced; Hypertension - drug therapy; Hypertension - urine; Infusion Pumps; Intracellular signalling; Kidneys; Lipidomics; Lipids; Lipids - urine; Manufacturers; MARCKS; MARCKS protein; Membranes; Metabolism; Mice; Microfilament Proteins - metabolism; miRNA; Proteins; Reactive oxygen species; Reactive Oxygen Species - metabolism; Reagents; Renal cortex; ROS; Salt; salt-sensitive hypertension; Sodium Chloride, Dietary - adverse effects; Software; Spin Labels; Tempol; Urine
• ISSN: 2218-273X; 2218-273X
• DOI: 10.3390/biom11121804

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.