Arterial hypertension induced by saline overload: role of chloride anion

Abstract

A chronic saline (as sodium chloride) overload (SO) in the diet induces a renal inflammatory response and oxidative stress, which lead to the development of hypertension. The aim of this work was to demonstrate the hypothesis that chloride anion (Cl-), besides sodium cation (Na+), is involved in these inflammatory and oxidative responses. These alterations might be diminished if Cl- is replaced by other anion (like citrate), or if Na+ is replaced by other cations.Male Wistar rats were randomly divided into four experimental groups (n=8): control (C); SO (NaCl 8% W/W); high Na+ without Cl- (Na: Na3C6H5O7 11,8%); high Cl- without Na+ (Cl: CaCl2 3,80%; KCl 3,06% and MgCl2 1,30%). After three weeks, systolic blood pressure (SBP) was measured, and rats were housed in metabolic cages in order to collect 24-hour urine to assess renal function. Oxidative stress parameters were measured in renal cortex: TBARS production andantioxidant enzymes activities and expression:superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx). In all the experimental groups we observed a significant increase of diuresis (*p<0,05 versus C) while SBP was increased only in those rats fed with Cl- (mmHg, C:125±9; NaCl:164±8*; Na:133±4; Cl:152±7*). These changes were accompanied by an increase in TBARS production in renal cortex (mol TBARS/mg protein) (x10^12): C:1,30±0,10; NaCl:1,82±0,18*; Na:2,01±0,32*; Cl:1,91±0,34*. No changes were observed on the activity or expression of SOD and CAT. Despite the fact that GPx expression was unaltered, the enzyme activity was increased in those groups with Cl- (μmol GSSG/mg protein.min, C:1,34±0,14; NaCl:2,31±0,37*; Na:1,30±0,14; Cl:2,77±0,52*). These results suggest a relevant role of Cl- in the development of hypertension, independently on Na+. Saline overload, and both ions separately, induced lipid oxidative damage. Nevertheless, only Cl- salt diets produced an increase in GPx activity, resulting in a high prooxidant state in kidney.