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Angiotensin II Type 2-Receptor Agonist C21 Reduces Proteinuria and Oxidative
Stress in Kidney of High-Salt-Fed Obese Zucker Rats
#MMPMID27021008
Patel SN
; Ali Q
; Hussain T
Hypertension
2016[May]; 67
(5
): 906-15
PMID27021008
show ga
Oxidative and nitrosative stress have been implicated in high-sodium diet
(HSD)-related hypertensive renal injury. In this study, we investigated
angiotensin II type 2-receptor-mediated renoprotection in obese Zucker rats fed
HSD. Obese Zucker rats were fed normal sodium diet or HSD 4%, for 14 days,
with/without angiotensin II type 2-receptor agonist C21, delivered subcutaneously
via osmotic pump, 1 mg/kg per day. Compared with normal sodium diet controls, HSD
rats exhibited increase in cortical nicotinamide adenine dinucleotide phosphate
oxidase activity, urinary H2O2, and 8-isoprostanes, which were associated with
severe glomerulosclerosis, interstitial fibrosis, decline in estimated glomerular
filtration rate, and an increase in urinary leak and activity of
N-acetyl-?-D-glucosaminidase, a lysosomal enzyme and a marker of tubular damage.
These changes were improved by C21 treatment. Cortical expression of endothelial
nitric oxide synthase, phospho-endothelial nitric oxide synthase (Ser(1177)), and
plasma nitrites were reduced after HSD intake, whereas nitrosative stress
(3-nitrotyrosine) and enzymatic defense (superoxide dismutase-to-catalase
activity) remained unaltered. However, C21 preserved plasma nitrites in HSD-fed
obese Zucker rat. C21 treatment reduced protein-to-creatinine,
albumin-to-creatinine, as well as fractional excretion of protein and albumin in
HSD-fed obese Zucker rat, which is independent of changes in protein recycling
receptors, megalin, and cubilin. HSD intake also altered renal excretory and
reabsorptive capacity as evident by elevated plasma urea nitrogen-to-creatinine
and fractional excretion of urea nitrogen, and reduced urine-to-plasma
creatinine, which were modestly, but insignificantly, improved by C21 treatment.
Together results demonstrate that angiotensin II type 2-receptor activation
protects against HSD-induced kidney damage in obesity plausibly by reducing
nicotinamide adenine dinucleotide phosphate oxidase activity and rescuing
nitrites.
|Acute Kidney Injury/etiology/*pathology
[MESH]
|Analysis of Variance
[MESH]
|Angiotensin II Type 1 Receptor Blockers/administration & dosage/*pharmacology
[MESH]
|Animals
[MESH]
|Biopsy, Needle
[MESH]
|Blood Pressure/drug effects
[MESH]
|Disease Models, Animal
[MESH]
|Hypertension/physiopathology/prevention & control
[MESH]
|Immunohistochemistry
[MESH]
|Male
[MESH]
|Multivariate Analysis
[MESH]
|Nitric Oxide Synthase Type III/drug effects/metabolism
[MESH]
|Oxidative Stress/*drug effects
[MESH]
|Proteinuria/drug therapy/*prevention & control
[MESH]
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