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.