Endogenous lithium clearance: a diagnostic method of assessing sodium sensitivity in hypertension. Methodological and clinical implications

Cwynar, Marcin; Stompór, Tomasz; Bartoń, H.; Grodzicki, Tomasz

doi:10.5603/kp.2014.0002

Cited by 1 publication

(1 citation statement)

References 53 publications

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“…Numerous studies have reported the association of obesity with increased reabsorption of Na + in proximal tubules [59,60,61], impaired pressure natriuresis, and then hypertension [29]. Endogenous cardiotonic steroids (CTS) in humans and rodents [57,62], can signal through Na/K-ATPase, regulating renal salt handling in the proximal tubules [11,13,16] and contributing to salt-sensitive hypertension [12,15].…”

Section: Discussionmentioning

confidence: 99%

Metabolic Syndrome and Salt-Sensitive Hypertension in Polygenic Obese TALLYHO/JngJ Mice: Role of Na/K-ATPase Signaling

Yan

Wang

Chaudhry

et al. 2019

IJMS

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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.

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