Department of Physiology and Functional Genomics, University of Florida, Gainesville, FL 32610, USA.
Department of Physiological Sciences and Center for Environmental and Human Toxicology, University of Florida, Gainesville, FL 32610, USA.
Biomolecules. 2021 Dec 1;11(12):1804. 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.
盐敏感型高血压是由于高盐饮食后血压升高引起的，与活性氧（ROS）的产生增加有关。ROS 已知会增加上皮钠通道（ENaC）的活性，因此，它们对钠潴留和血压升高有间接影响。细胞外囊泡（EVs）携带各种分子，包括蛋白质、microRNAs 和脂质，在健康和疾病中发挥着细胞间通讯和细胞内信号转导的作用。我们研究了抗氧化剂 Tempol 在盐敏感型高血压 129Sv 小鼠中的应用后，EV 脂质、尿电解质、渗透压、血压以及肾脏 ENaC 及其衔接蛋白 MARCKS/MARCKS Like Protein 1 (MLP1) 的表达变化。我们的结果表明，Tempol 输注可降低高血压 129Sv 小鼠肾脏皮质的收缩压和 ENaC 的α亚单位和 MARCKS 的蛋白表达。我们的脂质组学数据显示，Tempol 处理后，这些小鼠的尿 EV 中二酰基甘油和单酰基甘油含量增加，而神经酰胺、二氢神经酰胺和三酰基甘油含量减少。这些数据将为我们理解涉及抑制 ROS 以缓解盐敏感型高血压的机制提供新的见解。
