Epithelial Sodium Channel Alpha Subunit (αENaC) Is Associated with Inverse Salt Sensitivity of Blood Pressure

Biomedicines

Peng Xu¹  Wei Yue¹  Robin A. Felder¹  John J. Gildea¹  Robert M. Carey²  Mahabuba Akhter²  Anastasia V. Sudarikova³  Daria V. Ilatovskaya³  Pedro A. Jose⁴ 

[1] Department of Pathology, University of Virginia Health System, Charlottesville, VA 22903, USA;Division of Endocrinology and Metabolism, Department of Medicine, University of Virginia Health System, Charlottesville, VA 22903, USA;Division of Nephrology, Department of Medicine, Medical University of South Carolina, Charleston, SC 29425, USA;School of Medicine and Health Sciences, The George Washington University, Washington, DC 20052, USA;

关键词: aldosterone;    ENaC;    inverse salt sensitivity;    patch clamp;    salt resistance;    salt sensitivity;   

DOI  :  10.3390/biomedicines10050981

来源: DOAJ

【 摘 要 】

Salt sensitivity of blood pressure (BP) refers to an increase in BP following an increase in dietary salt, which is associated with increased incidence of cardiovascular disease and early death. However, decreased sodium intake also increases mortality and morbidity. Inverse salt sensitivity (ISS), defined as a paradoxical increase in BP on a low-salt diet, about 11% of the population, may be the cause of this phenomenon. The epithelial sodium channel (ENaC) is a major regulator of sodium reabsorption in the kidney. In this study, human renal tubular epithelial cells (hRTC) were cultured from the urine of phenotyped salt study participants. αENaC expression was significantly lower in ISS than salt resistant (SR) hRTC, while ENaC-like channel activity was dramatically increased by trypsin treatment in ISS cells analyzed by patch clamp. αENaC expression was also decreased under high-salt treatment and increased by aldosterone treatment in ISS cells. Moreover, the αENaC variant, rs4764586, was more prevalent in ISS. In summary, αENaC may be associated with ISS hypertension on low salt. These findings may contribute to understanding the mechanisms of ISS and low salt effect on morbidity and mortality.

【 授权许可】

Unknown