title: Telmisartan protects 5/6 Nx rats against renal injury by enhancing nNOS-derived NO generation via regulation of PPARγ signaling.
abstract: A 5/6 nephrectomized (Nx) rat model was employed to address the impact of telmisartan on CKD related renal injury and the underlying molecular mechanisms. It was noted that telmisartan provided protection for rats against 5/6 Nx induced lethality. Telmisartan treated 5/6 Nx rats manifested improved renal function as characterized by the higher GFR but lower urinary albumin, BUN and Scr as compared with that of control rats. Telmisartan treatment also significantly decreased systolic blood pressure and alleviated glomerulosclerosis and interstitial fibrosis. Mechanistic studies revealed that telmisartan possesses the capability to increase NO generation in the kidney. Further studies demonstrated that telmisartan promotes PPARγ expression, by which it specifically enhances nNOS expression in the kidneys after 5/6 Nx insult. Particularly, blockade of PPARγ signaling by GW9662 abolished the protective effect conferred by telmisartan, indicating that telmisartan induction of renal nNOS expression along with NO generation is dependent on PPARγ signaling. Together, our data support that telmisartan could be a promising drug for treatment of chronic kidney diseases in diverse clinical settings.
authors.affiliation: Department of Nephrology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology Wuhan 430030, China ; Department of Nephrology, Wuhan Integrated TCM and Western Medicine Hospital, Tongji Medical College, Huazhong University of Science and Technology Wuhan 430030, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Zou
authors.affiliation: Department of Nephrology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology Wuhan 430030, China ; Department of Nephrology, The Fifth City Hospital of Wuhan Wuhan 430050, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: He
authors.affiliation: Department of Nephrology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology Wuhan 430030, China.
authors.forename: Yue-Qiang
authors.initials: YQ
authors.lastname: Li
authors.affiliation: Department of Nephrology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology Wuhan 430030, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Han
authors.affiliation: Department of Nephrology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology Wuhan 430030, China.
authors.forename: Zu-Fu
authors.initials: ZF
authors.lastname: Ma
authors.affiliation: Department of Nephrology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology Wuhan 430030, China.
authors.forename: Xiao-Cheng
authors.initials: XC
authors.lastname: Liu
authors.affiliation: Department of Nephrology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology Wuhan 430030, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Zeng
authors.affiliation: Department of Nephrology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology Wuhan 430030, China.
authors.forename: Jv-Fang
authors.initials: JF
authors.lastname: Shao
authors.affiliation: Department of Nephrology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology Wuhan 430030, China ; The Center for Biomedical Research, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology Wuhan 430030, China.
authors.forename: Yan-Chao
authors.initials: YC
authors.lastname: Guo
authors.affiliation: The Center for Biomedical Research, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology Wuhan 430030, China.
authors.forename: Xiao-Yu
authors.initials: XY
authors.lastname: He
authors.affiliation: The Center for Biomedical Research, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology Wuhan 430030, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Yang
authors.affiliation: Department of Nephrology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology Wuhan 430030, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Xu
authors.affiliation: The Center for Biomedical Research, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology Wuhan 430030, China.
authors.forename: Cong-Yi
authors.initials: CY
authors.lastname: Wang
authors.affiliation: Department of Nephrology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology Wuhan 430030, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Yao
keywords: 5/6 nephrectomy; CKD; PPARγ; nNOS; telmisartan