High salt-induced weakness of anti-oxidative function of natriuretic peptide receptor-C and podocyte damage in the kidneys of Dahl rats

Abstract

Background: Atrial natriuretic peptide (ANP) and its natriuretic peptide receptors A (NPR-A) and C (NPR-C) are involved in the regulation of physiological and pathophysiological process of blood pressure. The present study aimed to determine the role of NPR-C in the development of salt-sensitive hypertension. Methods: The Dahl salt-sensitive (DS) and salt-resistant (DR) rats were used in this study. Animals were matched according to their age and weight, and then placed on either a high-salt (HS, 8%) or a normal-salt (NS, 0.4%) diet for 6 weeks randomly using random number table. The systolic blood pressure (SBP), plasmatic sodium concentration (PLNa), urinary sodium excretion (UVNa), and serum creatinine concentration (Scr) were measured. The concentration of ANP in blood and tissues (heart and kidney) was detected by enzyme-linked immunosorbent assay. The expression of ANP, NPR-A, and NPR-C in kidney was evaluated with western blot analysis. Regarding renal redox state, the concentration changes in malondialdehyde (MDA), lipofuscin, nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (Nox), and nitric oxide synthase (NOS) in kidney were detected by a spectrophotometric method. The kidney damage was evaluated using pathological techniques and the succinodehydrogenase (SDHase) examination. Furthermore, after an intra-peritoneal injection of C-atrial natriuretic peptide (ANP)4–23 (C-ANP4–23), an NPR-C receptor agonist, the SBP, biochemical values in blood and urine, and renal redox state were evaluated. The paired Student's t test and analysis of variance followed by the Bonferroni test were performed for statistical analyses of the comparisons between two groups and multiple groups, respectively. Results: The baseline SBP in all groups was within the normal range. At the end of the 6-week experiment, HS diet significantly increased the SBP in DS rats from 116.63 ± 2.90 mmHg to 162.25 ± 2.15 mmHg (t = −10.213, P < 0.001). The changes of SBP were not significant in DS rats on an NS diet and DR rats on an NS diet or on an HS diet (all P > 0.05). The significant increase of PLNa, UVNa, and Scr related to an HS diet was found in both DS and DR rats (all P < 0.05). However, significant changes in the concentration (t = −21.915, P < 0.001) and expression of renal ANP (t = −3.566, P = 0.016) and the expression of renal NPR-C (t = 5.864, P = 0.002) were only observed in DS hypertensive rats. The significantly higher desmin immunochemical staining score (t = −5.715, P = 0.005) and mitochondrial injury score (t = −6.325, P = 0.003) accompanied by the lower SDHase concentration (t = 3.972, P = 0.017) revealed mitochondrial pathologic abnormalities in podocytes in DS rats with an HS diet. The distinct increases of MDA (t = −4.685, P = 0.009), lipofuscin (t = −8.195, P = 0.001), and Nox (t = −12.733, P < 0.001) but not NOS (t = −0.328, P = 0.764) in kidneys were also found in DS hypertensive rats. C-ANP4–23 treatment significantly decreased the SBP induced by HS in DS rats (P < 0.05), which was still higher than NS groups with the vehicle or C-ANP4–23 treatment (P < 0.05). Moreover, the HS-induced increase of MDA, lipofuscin, Nox concentrations, and Nox4 expression in DS rats was significantly attenuated by C-ANP4–23 treatment as compared with those with HS diet and vehicle injection (all P < 0.05). Conclusions: The results indicated that the renal NPR-C might be involved in the salt-sensitive hypertension through the damage of mitochondria in podocytes and the reduction of the anti-oxidative function. Hence, C-ANP4–23 might serve as a therapeutic agent in treating salt-sensitive hypertension.

Effect of the Natural Cat and Dog Liquid Additives on 3% Salt Fed Rats

“…The urine volume, pH and specific gravity of rats were not significantly different between the treatment groups. The rat's urine volume, pH and specific gravity values were significantly influenced from the treatments which were in agreement with the other studies [11][12][13][14][15][16][17]. The results of urine biochemical analysis of the rats are shown in Table 2.…”

Cosinor-rhythmometry for 24-h urinary sodium, potassium, creatinine excretion in the Chinese adult population

“…[ 22 ] Peripheral molecular clocks are involved in the regulation of circadian blood pressure, as well as sodium and potassium homeostasis by kidneys. [ 23 , 24 ] Early researches have reported that the excretion of sodium, potassium, and water by renal metabolism followed a strong circadian pattern in both humans and non-human primates, independently of the time of day when food and water were ingested. [ 20 , 25 ] This study verified this circadian rhythm of urinary excretion in healthy adults, which might help improve the prediction formulas for 24-h urinary sodium excretion using single spot urine samples.…”

Phyllanthus amarus attenuated derangement in renal-cardiac function, redox status, lipid profile and reduced TNF-α, interleukins-2, 6 and 8 in high salt diet fed rats

“…This phenomenon might be linked to the observed decrease in antioxidant enzymes activity vis-a-vis catalase and glutathione (GSH) in HSD-treated animals. Depleted level of GSH can be caused by increased generation of ROS, resulting in a buoyed level of malondialdehyde, TNF-α, interleukin-6 (IL-6), and deranged functioning of the immune system [46,47,48,49]. HSD also up-regulates inflammatory molecules like vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule1 (ICAM-1), and nuclear factor-kappa B (NF-κB) [46].…”