Abstract
BACKGROUNDObesity is a public health problem, associated with salt sensitive hypertension, kidney inflammation, and fibrosis. N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) is a tetra peptide with anti-inflammatory and anti-fibrotic properties. However, its effect on preventing kidney damage in obesity is unknown. We hypothesized that Zucker obese (ZO) rats on a high-salt (HS) diet develop renal damage, inflammation, fibrosis, and this is prevented with Ac-SDKP treatment.METHODSZucker lean (ZL) and ZO rats (8 weeks old) were treated with Ac-SDKP (1.6 mg/kg/day) while maintained on either a normal-salt (NS; 0.4%) or HS (4%) diet for 8 weeks. Systolic blood pressure (SBP), albuminuria, renal inflammation, and fibrosis were evaluated.RESULTSHS diet increased macrophage infiltration in the kidneys of both ZL and ZO rats but was significantly higher in ZO rats receiving the HS diet (ZL + NS, 13.9 ± 1.3 vs. ZL + HS, 19.14 ± 1.5 and ZO + NS, 25.5 ± 1.4 vs. ZO + HS, 87.8 ± 10.8 cells/mm2; P < 0.05). Ac-SDKP prevented macrophage infiltration in ZO rats (ZO + HS + Ac-SDKP, 32.18 ± 2.4 cells/mm2; P < 0.05). Similarly, glomerulosclerosis, cortical, and medullary interstitial fibrosis were increased in ZO rats fed the HS diet, and Ac-SDKP attenuated these alterations (P < 0.05). SBP was increased in ZO rats fed the HS diet (ZO + NS, 121.3 ± 8.9 vs. ZO + HS, 164 ± 6.9 mm Hg; P < 0.05), and it was significantly decreased with Ac-SDKP treatment (ZO + HS + Ac-SDKP, 144.05 ± 14.1 mm Hg; P = 0.004). Albuminuria was higher in ZO rats than in ZL rats; however, neither HS nor Ac-SDKP treatment affected it.CONCLUSIONSAc-SDKP treatment in ZO rats fed a HS diet prevented renal damage by reducing inflammation, fibrosis, and SBP.
Highlights
Obesity is a public health problem, associated with salt sensitive hypertension, kidney inflammation, and fibrosis
Glomerulosclerosis, cortical, and medullary interstitial fibrosis were increased in Zucker obese (ZO) rats fed the HS diet, and Ac-SDKP attenuated these alterations (P < 0.05)
Systolic blood pressure (SBP) was increased in ZO rats fed the HS diet (ZO + NS, 121.3 ± 8.9 vs. ZO + HS, 164 ± 6.9 mm Hg; P < 0.05), and it was significantly decreased with Ac-SDKP treatment (ZO + HS + Ac-SDKP, 144.05 ± 14.1 mm Hg; P = 0.004)
Summary
Zucker lean (ZL) and ZO rats (8 weeks old) were treated with Ac-SDKP (1.6 mg/kg/day) while maintained on either a normal-salt (NS; 0.4%) or HS (4%) diet for 8 weeks. Rats were allowed 7 days to acclimatize to the new environment before the experiments were performed. ZL and ZO rats (8 weeks old) were placed on either a normal-salt (NS; 0.4% NaCl) or HS (4% NaCl) diet (Teklad diets, Harlan, Madison, WI) and were subcutaneously infused with vehicle (0.01 N acetic acid 0.9% saline solution) or Ac-SDKP (1.6 mg/kg/day) for 8 weeks using osmotic mini-pumps (Alzet, Cupertino, CA). Blood pressure was measured weekly with a tail-cuff method; 24-hour urine collection was carried out for urinary Ac-SDKP, albumin, and sodium excretion. At the end of the experiment, the animals were sacrificed, and tissues were weighed and collected for biochemical and histological studies
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