RENAL OXIDATIVE STRESS IN A MODEL OF HYPERTENSION INDUCED BY SALINE OVERLOAD: ROLE OF CHLORIDE ANION

Objective: A chronic saline overload in the diet induces a renal inflammatory response and oxidative stress, leading to hypertension development. Our aim was to demonstrate that chloride anion (Cl-), besides sodium cation (Na+), is involved in these inflammatory and oxidative responses. These alterations might be reduced if Cl- is replaced by other anion (like citrate), or if Na+ is replaced by other cations. Design and method: Male Wistar rats were divided into four groups (n = 8): control (C); NaCl 8%W/W; high Na+ without Cl- (Na: sodium citrate 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 determined in renal cortex: TBARS production and antioxidant enzymes activities and expression of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx). Results: In all 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) (x1012): 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 GPx expression being unaltered, its activity was increased in those groups with Cl- (micromol oxidized glutathione/mg protein.min, C:1,34 ± 0,14; NaCl:2,31 ± 0,37∗; Na:1,30 ± 0,14; Cl:2,77 ± 0,52∗). Conclusions: A high salt intake as sodium chloride increased SBP and water, sodium and chloride urinary excretion after 3 weeks of treatment. These changes were associated with an increase in oxidative stress parameters in renal cortex (mainly TBARS production and GPx activity). Only chloride salts could increase diuresis and induce an increase in SBP (compared with C) but reaching lower values than NaCl group. Additionally, chloride salts were able to increase oxidative stress parameters in renal cortex as NaCl group. These findings suggest that chloride component in the diets can be crucial to determine a higher prooxidant state in the kidney, rather than the sodium component in salt diets.