Protective effect of aliskiren on renal injury in AGT-REN double transgenic hypertensive mice
YANG Xiao-Ling1,2, CHEN Yan-Yan3, ZHAO Hua1, ZHANG Bo-Yang1, ZHANG Xiao-Fu1, LI Xiao-Jie1, YANG Xiu-Hong1,2,*
1School of Basic Medicine, North China University of Science and Technology, Tangshan 063000, China;2Hebei Key Laboratory of Basic Medicine for Chronic Diseases, Tangshan 063000, China;3Central Official Hospital, Beijing 100091, China
Abstract
This study aims to investigate the effects of renin inhibitor aliskiren on kidney injury in human angiotensinogen-renin (AGT-REN) double transgenic hypertensive (dTH) mice and explore its possible mechanism. The dTH mice were divided into hypertension group (HT group) and aliskiren intervention group (HT+Aliskiren group), while wild-type C57BL/6 mice were served as the control group (WT group). Blood pressure data of mice in HT+Aliskiren group were collected after 28 d of subcutaneous penetration of aliskiren (20 mg/kg), and the damage of renal tissue structure and collagen deposition were observed by HE, Masson and PAS staining. The ultrastructure of kidney was observed by transmission electron microscope. Coomassie bright blue staining and biochemical analyzer were used to detect renal function injury. The expression of renin-angiotensin system (RAS) was determined by ELISA and immunohistochemistry. The contents of superoxide dismutase (SOD) and malondialdehyde (MDA) in kidney were determined by chemiluminescence method. The content of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunit p47phox, inducible nitric oxide synthase (iNOS), 3-nitrotyrosine (3-NT), NADPH oxidase 2 (NOX2) and NADPH oxidase 4 (NOX4) were detected by Western blot analysis. The results showed that compared with WT group, the blood pressure of mice in HT group was significantly increased. The renal tissue structure in HT group showed glomerular sclerosis, severe interstitial tubular injury, and increased collagen deposition. In addition, 24 h urinary protein, serum creatinine and urea levels increased. Serum and renal tissue levels of angiotensin II (Ang II) were increased, serum angiotensin-(1-7) [Ang-(1-7)] expression was decreased, and renal Ang-(1-7) expression was elevated. The expressions of ACE, Ang II type 1 receptor (AT1R) and MasR in renal tissue were increased, while the expression of ACE2 was decreased. MDA content increased, SOD content decreased, and the expressions of p47phox, iNOS, 3-NT, NOX2 and NOX4 were increased. However, aliskiren reduced blood pressure in dTH mice, improved renal structure and renal function, reduced Ang II and Ang-(1-7) levels in serum and renal tissue, reduced the expression of ACE and AT1R in renal tissue, increased the expression of ACE2 and MasR in renal tissue, and decreased the above levels of oxidative stress indexes in dTH mice. These results suggest that aliskiren may play a protective role in hypertensive renal injury by regulating the balance between ACEAng II-AT1R and ACE2-Ang-(1-7)-MasR axes and inhibiting oxidative stress.
Key words: Hypertension; aliskiren; renin-angiotensin system; renin inhibitor; kidney injury
Received: Accepted:
Corresponding author: 杨秀红 E-mail:
DOI: 10.13294/j.aps.2025.0046
Citing This Article:
YANG Xiao-Ling, CHEN Yan-Yan, ZHAO Hua, ZHANG Bo-Yang, ZHANG Xiao-Fu, LI Xiao-Jie, YANG Xiu-Hong. Protective effect of aliskiren on renal injury in AGT-REN double transgenic hypertensive mice. Acta Physiol Sin 2025; 77 (3): 408-418 (in Chinese with English abstract).