Alamandine alleviates hypertension and renal damage via oxidative-stress attenuation in Dahl rats

Figures

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  Fig. 1. Alamandine (Ala) alleviated renal dysfunction and hypertension of Dahl salt-sensitive (SS) rats induced by high-salt diet. a Ala (500 and 5000 μg/kg/d) inhibited the increases in BUN, Cr, and CysC in Dahl SS rats; (b) Ala (500 μg/kg/d) inhibited the increases in the systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP) in Dahl SS rats. The data are expressed as mean ± standard error of the mean (SEM); n = 8 in each group. *P < 0.05, **P < 0.01, ***P < 0.001, and ****P < 0.0001; #P < 0.05 vs. Dahl SS-saline group.

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  Fig. 2. Alamandine (Ala) alleviated renal damage of Dahl salt-sensitive (SS) rats induced by high-salt diet. a The increased renal fibrosis in Dahl SS rats induced by high-salt diet was inhibited by Ala (200 X). b The increase of the TUNEL-positive cell number in the kidney of Dahl SS rats induced by high-salt diet was suppressed by Ala (200 X). c The increase of the Bax-positive cell number in the kidney of Dahl SS rats induced by high-salt diet was suppressed by Ala (200 X). d The increase of the c-caspase3-positive cell number in the kidney of Dahl SS rats induced by high-salt diet was suppressed by Ala (200 X). The data are expressed as mean ± standard error of the mean (SEM); n = 8 in each group. *P < 0.05, **P < 0.01, ***P < 0.001, and ****P < 0.0001; #P < 0.05 vs. Dahl SS-saline group.

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  Fig. 3. Alamandine (Ala) alleviated renal tubular cell damage induced by sodium chloride (NaCl). a Ala (1.0 and 10 µg/mL) inhibited the increases of KIM-1 and NGAL in HK-2 cells induced by NaCl. b Ala (1.0 µg/mL) inhibited the increases in cleaved (c)-caspase3, c-caspase8, and c-poly(ADP-ribose) polymerase (PARP) in HK-2 cells induced by NaCl. The data are expressed as mean ± standard error of the mean (SEM); n = 8 (a) or 4 (b) in each group. *P < 0.05, **P < 0.01, ***P < 0.001, and ****P < 0.0001.

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  Fig. 4. Alamandine (Ala) alleviated renal oxidative stress induced by sodium chloride (NaCl). a Ala reversed the decreases of superoxide dismutase (SOD) activity and glutathione peroxidase (GSH) level, and the increases in malonaldehyde (MDA) and superoxide anions in the kidney of Dahl salt-sensitive (SS) rats induced by high-salt diet. b The increase of the 8-OHdG-positive cell number in the kidney of Dahl SS rats induced by high-salt diet was suppressed by Ala (200 X). c Ala reversed the decreases of SOD activity and GSH level, and the increases in MDA and superoxide anions in HK-2 cells induced by NaCl. d Ala inhibited the rise in glutathione S-transferase (GST)—Ras-related C3 botulinum-toxin substrate 1 (Rac1), p22phox, p47phox, and NADPH oxidase 4 (NOX4) in HK-2 cells induced by NaCl. The data are expressed as mean ± standard error of the mean (SEM); n = 8 (a) or 4 (b) in each group. *P < 0.05, **P < 0.01, ***P < 0.001, and ****P < 0.0001.

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  Fig. 5. Oxidative-stress enhancement reversed the alleviating effects of alamandine (Ala) on renal tubular cell damage induced by sodium chloride (NaCl). Diethyldithiocarbamate (DETC) reversed the inhibitory effect of Ala on the increase in cleaved (c)-caspase-3, c-caspase-8, and c-poly(ADP-ribose) polymerase (PARP) induced by NaCl in HK-2 cells. The data are expressed as mean ± standard error of the mean (SEM); n = 4 in each group. *P < 0.05, **P < 0.01, ***P < 0.001, and ****P < 0.0001.

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  Fig. 6. PKC signaling pathway was involved in the effects of alamandine (Ala) on attenuating apoptosis of renal tubular cell damage induced by sodium chloride (NaCl). a Ala inhibited the increase of PKC in the HK-2 cells induced by NaCl. b PKC overexpression reversed the attenuating effects of Ala on the increases of cleaved (c)-caspase3, c-caspase8, and c-poly(ADP-ribose) polymerase (PARP) induced by NaCl in HK-2 cells. The data are expressed as mean ± standard error of the mean (SEM); n = 4 in each group. *P < 0.05, **P < 0.01, ***P < 0.001, and ****P < 0.0001.