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- Title
Metabolic Syndrome and Salt-Sensitive Hypertension in Polygenic Obese TALLYHO/JngJ Mice: Role of Na/K-ATPase Signaling.
- Authors
Yan, Yanling; Wang, Jiayan; Chaudhry, Muhammad A.; Nie, Ying; Sun, Shuyan; Carmon, Jazmin; Shah, Preeya T.; Bai, Fang; Pratt, Rebecca; Brickman, Cameron; Sodhi, Komal; Kim, Jung Han; Pierre, Sandrine; Malhotra, Deepak; Rankin, Gary O.; Xie, Zi-jian; Shapiro, Joseph I.; Liu, Jiang
- Abstract
We have demonstrated that Na/K-ATPase acts as a receptor for reactive oxygen species (ROS), regulating renal Na+ handling and blood pressure. TALLYHO/JngJ (TH) mice are believed to mimic the state of obesity in humans with a polygenic background of type 2 diabetes. This present work is to investigate the role of Na/K-ATPase signaling in TH mice, focusing on susceptibility to hypertension due to chronic excess salt ingestion. Age-matched male TH and the control C57BL/6J (B6) mice were fed either normal diet or high salt diet (HS: 2, 4, and 8% NaCl) to construct the renal function curve. Na/K-ATPase signaling including c-Src and ERK1/2 phosphorylation, as well as protein carbonylation (a commonly used marker for enhanced ROS production), were assessed in the kidney cortex tissues by Western blot. Urinary and plasma Na+ levels were measured by flame photometry. When compared to B6 mice, TH mice developed salt-sensitive hypertension and responded to a high salt diet with a significant rise in systolic blood pressure indicative of a blunted pressure-natriuresis relationship. These findings were evidenced by a decrease in total and fractional Na+ excretion and a right-shifted renal function curve with a reduced slope. This salt-sensitive hypertension correlated with changes in the Na/K-ATPase signaling. Specifically, Na/K-ATPase signaling was not able to be stimulated by HS due to the activated baseline protein carbonylation, phosphorylation of c-Src and ERK1/2. These findings support the emerging view that Na/K-ATPase signaling contributes to metabolic disease and suggest that malfunction of the Na/K-ATPase signaling may promote the development of salt-sensitive hypertension in obesity. The increased basal level of renal Na/K-ATPase-dependent redox signaling may be responsible for the development of salt-sensitive hypertension in polygenic obese TH mice.
- Subjects
METABOLIC syndrome; HIGH-salt diet; SYSTOLIC blood pressure; FLAME photometry; HYPERTENSION; MICE
- Publication
International Journal of Molecular Sciences, 2019, Vol 20, Issue 14, p3495
- ISSN
1661-6596
- Publication type
Article
- DOI
10.3390/ijms20143495