2. Academic Validation
  3. Canagliflozin and irbesartan ameliorate renal fibrosis via the TGF-β1/Smad signaling pathway in Dahl salt-sensitive rats

Canagliflozin and irbesartan ameliorate renal fibrosis via the TGF-β1/Smad signaling pathway in Dahl salt-sensitive rats

  • J Int Med Res. 2023 Oct;51(10):3000605231206289. doi: 10.1177/03000605231206289.
Jianlong Zhai 1 2,  Zhongli Wang 1 3,  Tingting Zhang 4,  Lili He 4,  Sai Ma 5,  Qingjuan Zuo 4,  Guorui Zhang 1 6,  Xinyu Wang 7,  Yifang Guo 1 4
Affiliations

Affiliations

  • 1 Department of Internal Medicine, Hebei Medical University, Shijiazhuang, China.
  • 2 Department of Cardiology, Hebei General Hospital, Shijiazhuang, China.
  • 3 Department of Medical Examination Center, Hebei General Hospital, Shijiazhuang, China.
  • 4 Department of Geriatric Cardiology, Hebei General Hospital, Shijiazhuang, China.
  • 5 Department of Pain Medicine, Hebei General Hospital, Shijiazhuang, China.
  • 6 Department of Cardiology, The Third Hospital of Shijiazhuang City Affiliated to Hebei Medical University, Shijiazhuang, China.
  • 7 Department of Internal Medicine, Hebei North University, Zhangjiakou, China.
PMID: 37862678 DOI: 10.1177/03000605231206289
Abstract

Objectives: This study assessed the antifibrotic effects of canagliflozin, with or without irbesartan, on renal injury in Dahl salt-sensitive (SS) rats fed a high-salt (HS) diet.

Methods: After the preconditioning stage, Dahl SS rats (n = 47) were divided into five experimental groups as follows: low-salt (LS, n = 7), HS (n = 10), HS with canagliflozin (n = 10), HS with irbesartan (n = 10), and HS with canagliflozin and irbesartan (n = 10).

Results: The HS diet increased systolic blood pressure (SBP), renal fibrosis, fibrotic protein expression, and transforming growth factor-β1 (TGF-β1)/SMAD2/3 pathway protein expression compared with the findings in the LS group. Irbesartan reduced SBP and slowed the loss of renal function. Canagliflozin significantly reduced body weight and renal fibrosis and suppressed the TGF-β1/SMAD2/3 pathway. The combined therapy exerted better renoprotective effects on all outcome parameters.

Conclusions: These results indicate that canagliflozin and irbesartan exert different effects on renal injury in SS hypertensive rats, and the combined regimen could have stronger effects than either monotherapy.

Keywords

Dahl salt-sensitive rat; Smad2/3; angiotensin II receptor blocker; blood pressure; hypertension; renal fibrosis; sodium-glucose cotransporter 2 inhibitor; transforming growth factor-β1.

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