Participation of Chloride Channels in Cardiovascular and Kidney Health. Effects of High Chloride Diets on Blood Pressure in an Experimental Model of Saline Overload

pp. 130-138

Abstract

Background: Excessive consumption of salt (sodium chloride, NaCl) in the diet leads to the development of hypertension (HTN) and target organ damage. It is known that the ClC-K1 and ClC-5 channels are essential regulators of the chloride (Cl-) anion, but the contribution of this anion to salt-harmful effects remains unknown.

Objective: The aim of this study was to evaluate the participation of Cl- in the renal inflammatory and oxidative response and in the development of HTN.

Methods: Male Wistar rats were divided into four groups (n=8/group) and fed with different diets for 3 weeks: control (C
group); NaCl 8% (NaCl group); high Na+ diet: sodium citrate (Na3C6H5O7) 11.8% (Na group); high Cl- diet: calcium chloride (CaCl2) 3.80%, potassium chloride (KCl) 3.06% and magnesium chloride (MgCl2) 1.30% (Cl group). Systolic blood pressure (SBP), renal function, oxidative stress and inflammation markers in the renal cortex, and renal expression of the chloride ClC-K1 and ClC-5 channels were assessed.

Results: An increase in SBP, glutathione peroxidase (GPx) activity, and renal expression of nuclear factor kappa B (NFkB) and angiotensin II type 1 receptor (AT1R) were observed in the NaCl and Cl groups (p<0.05). The production of thiobarbituric acid reactive substances (TBARS) increased in the experimental groups compared with C. The expression of Parkinson disease protein 7 (PARK7) decreased in the Cl group compared with C (p< 0.05). The NaCl and Cl groups showed increased
expression of ClC-K1, while ClC-5 was reduced in the NaCl group compared with C (p<0.05)

Conclusion: Cl- would be co-responsible together with Na+ in triggering oxidative and inflammatory kidney damage and increasing blood pressure. This indicates the importance of reducing the intake of both ions as a non-pharmacological preventive measure for the prevention and control of HTN. The role of ClC-K1 and ClC-5 channels as mediators of this process remains to be confirmed.

How to cite this article:

Rudi MJ, Kouyoumdzian NM, Kim M, Rukavina Mikusic NL, Lee HJ, Galleano M, et al. Participation of Chloride Channels in Cardiovascular and Kidney Health. Effects of High Chloride Diets on Blood Pressure in an Experimental Model of Saline Overload. Rev Argent Cardiol 2024;92:130-38.  http://dx.doi.org/10.7775/rac.v92.i2.20753