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Up-regulation of intrarenal renin-agiotensin system contributes to renal damage in high-salt induced hypertension rats
WU Hai-Yan, LIANG Yao-Xian, ZHENG Yi-Mu, BAI Qiong, ZHUANG Zhen, A La-Ta, ZHENG Dan-Xia, WANG Yue
2015, (1):
149-154.
PMID: 25686347
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Objective: To test the hypothesis that in a high-salt induced hypertension in normal rats, whether the changes of intrarenal renin-agiotensin system (RAS) play a critical role in renal damage and could be reflected by urinary angiotensinogen (AGT). Methods: In the study, 27 normotensive male Wistar-Kyoto rats were divided into control group [0.3% (mass faction) NaCl in chow, n=9, NS], high-salt diet group [8% (mass faction) NaCl in chow, n=9, HS] and high-salt diet with Losartan group [8% (mass faction) NaCl in chow and 20 mg/(kg·d) Losartan in gavages, n=9, HS+L)], and were fed for six weeks. The blood pressure was monitored and urine samples were collected every 2 weeks. AGTs in plasma, kidney and urine were measured by ELISA kits. The renal cortex expression of mRNA and protein of AGT were measured by Real-time PCR and immunohistochemistry (IHC). The renin activity and ANGⅡ were measured by radioimmunoassay (RIA) kits. Results: Compared with NS, the systolic blood pressure (SBP) [(156±2) mmHg vs. (133±3) mmHg, P<0.05] increased significantly at the end of the 2nd week, and the urinary protein [(14.07±2.84) mg/24 h vs. (7.62±3.02) mg/24 h, P<0.05] increased significantly at the end of the 6th week in HS. Compared with HS, there was no significant difference in SBP (P>0.05) but the proteinuria [(9.69±2.73) mg/24 h vs. (14.07±2.84) mg/24 h, P<0.01] decreased significantly in HS+L. Compared with NS, there was no significant difference in the plasma renin activity, angiotensinogen and ANGⅡ level in HS (P>0.05), but the renal cortex renin content [(8.72±1.98) ng/(mL·h) vs. (4.37±1.26) ng/(mL·h), P<0.05], AGT formation [(4.02±0.60) ng/mg vs. (2.59±0.42) ng/mg, P<0.01], ANGⅡ level [(313.8±48.76) pmol/L vs. (188.9±46.95) pmol/L, P<0.05] were increased significantly in HS, and the urinary AGT and ANGⅡ excretion rates increased significantly (P<0.05). Compared with HS, the plasma renin activity, angiotensinogen and ANGⅡ level were significantly increased (P<0.05), but the renal cortex renin content, AGT formation, ANGⅡ level significantly decreased (P<0.05), and the urinary AGT and ANGⅡ excretion rates decreased significantly in HS+L (P<0.05). The urinary AGT excretion rates were positively correlated with the AGT level in the renal cortex (P<0.05). Conclusion: Up-regulation of intarenal RAS may contribute to renal damage in high-salt induced hypertension rats. Urinary AGT may reflect the status of intrarenal RAS.