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

Abstract

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.

Lipid Profiles of Urinary Extracellular Vesicles Released during the Inactive and Active Phases of Aged Male Mice with Spontaneous Hypertension

“…After incubation on ice for 10 min, 2 mL methanol, and 0.9 mL methylene chloride were added and the solution was vortexed for 30 s. EquiSPLASH Lipidomix (Avanti Polar Lipids, Inc., Alabaster, AL, USA), a mixture of 13 deuterated lipids was used as an internal standard. The composition of the internal standard mixture was described in our previous publication [ 14 ]. The internal standard was diluted 5 times using cold methanol to adjust each deuterated lipid’s concentration to 20 µg·mL −1 , and then 50 µL was spiked into each sample.…”

“…Collectively, uEVs have been demonstrated to be enriched in important renal transport proteins including aquaporins [ 10 , 11 ] and epithelial sodium channels [ 12 , 13 ]. Recent studies have demonstrated that uEVs are a rich source of biomarkers and can be useful in the pathogenesis of hypertension [ 14 ]. Although the excretion of EVs into the urine varies on a myriad of stressors [ 15 , 16 ], drug treatments [ 17 ], temperature changes [ 18 ], and social habits [ 19 ], little is known about the excretion of EVs into the urine during the inactive and active phases of any animal or rodent model.…”

Metabolomics of Extracellular Vesicles: A Future Promise of Multiple Clinical Applications

“… 70 For serum-derived EVs are notable in bipolar disorder, 73 COVID-19, 74 Alzheimer’s disease, 50 , 75 The whole blood has been displayed on breast cancer. 47 Urine tissue are always applied to research on kidney and prostate, such as salt-sensitive hypertension, 78 and prostate cancer (PCa). 79 Auditory cell-derived EVs has been utilized in drug- and noise-related hearing loss.…”

Fetal lung regeneration using stem cell‐derived extracellular vesicles: A new frontier for pulmonary hypoplasia secondary to congenital diaphragmatic hernia

“…EVs carry cargo in the form of genetic material (small RNA species, including miRNAs), proteins, and lipids, and can transfer their heterogeneous cargo to target cells to induce biological responses 40 . For this reason, EVs have been considered as therapeutic agents for several conditions including those where multiple molecules and/or pathways are missing or dysregulated, such as asthma, chronic lung disease, diabetes, systemic hypertension, and cancer 41–49 …”

“…40 For this reason, EVs have been considered as therapeutic agents for several conditions including those where multiple molecules and/or pathways are missing or dysregulated, such as asthma, chronic lung disease, diabetes, systemic hypertension, and cancer. [41][42][43][44][45][46][47][48][49]…”