High‐salt intake reduces renal tissue levels of inflammatory cytokines in mice

Abstract

High salt (HS) intake is usually considered as an aggravating factor to induce inflammatory renal injury. However, the changes in the renal levels of inflammatory cytokines during HS intake is not yet clearly defined. We hypothesize that HS increases renal levels of tumor necrosis factor‐alpha (TNF‐α) and interleukin‐6 (IL‐6) but decreases interleukin‐10 (IL‐10; anti‐inflammatory cytokine) and these responses exacerbate in NO deficient conditions. Both wild‐type (WT) and endothelial NO synthase knockout (eNOSKO) mice (~8 weeks old, n = 6 in each group) were given normal‐salt (NS; 0.3% NaCl) and HS (4% NaCl) containing diets for 2 weeks. Systolic blood pressure (SBP) was determined by tail‐cuff plethysmography and urine collections were made using metabolic cages. Basal SBP was higher in eNOSKO than WT mice (131 ± 7 vs 117 ± 3 mmHg; p < .05). HS intake for 2 weeks increased SBP in eNOSKO (161 ± 5 mmHg) but not in WT mice. In NS groups, the cytokine levels in renal tissues (measured using ELISA kits and expressed in pg/mg protein) were significantly higher in eNOSKO than WT mice (TNF‐α, 624 ± 67 vs. 325 ± 73; IL‐6, 619 ± 106 vs. 166 ± 61; IL‐10, 6,087 ± 567 vs. 3,929 ± 378). Interestingly, these cytokine levels in HS groups were significantly less both in WT (TNF‐α, 114 ± 17; IL‐6, 81 ± 14; IL‐10, 865 ± 130) and eNOSKO (TNF‐α, 115 ± 18; IL‐6, 56 ± 7; IL‐10, 882 ± 141) mice. These findings indicate that HS induces downregulation of cytokines in the kidney. Such HS‐induced reduction in cytokines, particularly TNF‐α (a natriuretic agent), would facilitate more salt‐retention, and thus, leading to salt‐sensitive hypertension in NO deficient conditions.

Ajuga bracteosa Exerts Antihypertensive Activity in l-NAME-Induced Hypertension Possibly through Modulation of Oxidative Stress, Proinflammatory Cytokines, and the Nitric Oxide/Cyclic Guanosine Monophosphate Pathway

“…Throughout the experiment, the animals were given a standard diet and water. 30 To anaesthetize, on the terminal day (35th) of the treatment, sodium thiopental (70–90 mg kg –1 , i.p.) was administered to the rats.…”

“…Systolic blood pressure (SBP) was measured on day 0, followed by after week 1, 3, and 5. Throughout the experiment, the animals were given a standard diet and water . To anaesthetize, on the terminal day (35th) of the treatment, sodium thiopental (70–90 mg kg –1 , i.p.)…”

“…NO and cGMP levels were measured in serum samples using a colorimetric NO assay kit and cGMP enzyme-linked immunosorbent assay kits (ELISA) kits (Elabscience), respectively, as per the manufacturer’s protocols . Similarly, the levels of IL-6 and TNF-α in serum were measured by ELISA (Elabscience). , …”

“…The organ homogenates were centrifuged at 9000 g for 10 min at 4 °C. The supernatant was transferred to clean microcentrifuge tubes and stored at −80 °C until further analysis …”

“…31 Similarly, the levels of IL-6 and TNF-α in serum were measured by ELISA (Elabscience). 30,32 5.14. Estimation of Oxidative Stress Markers in Tissue Homogenates.…”