Telmisartan Ameliorates Hypertension‐Induced Kidney Damage by Restoring Glomerular Endothelial Barrier Function

ABSTRACT Hypertension‐induced renal injury arises from endothelial dysfunction and elevated glomerular permeability. Telmisartan, an Angiotensin II (Ang II) receptor blocker (ARB), is commonly used to treat hypertension and is known for its long‐lasting effects, as well as its antioxidant and anti‐inflammatory properties. However, the effects of Telmisartan on glomerular permeability are less well‐documented. This study investigates the protective effects of Telmisartan (TEL), an Ang II receptor blocker, on hypertension‐induced kidney damage. Using a mouse model of Angiotensin II/high salt (ANG/HS)‐induced hypertension, TEL treatment significantly reduced mean arterial pressure, alleviated renal fibrosis, and improved kidney function, as indicated by lower urinary albumin and serum creatinine levels. TEL also suppressed oxidative stress and reduced the expression of inflammatory markers interleukin‐6 (IL‐6) and tumor necrosis factor‐α (TNF‐α) in renal tissues. Furthermore, TEL restored the expression of the tight junction protein zonula occludens‐1 (ZO‐1) in the glomeruli, which was downregulated in ANG/HS‐treated mice. In vitro studies on human renal glomerular endothelial cells (HrGECs) confirmed that TEL reduced endothelial monolayer permeability and restored ZO‐1 expression, effects that were mediated by Krüppel‐like factor 4 (KLF4). These findings suggest that TEL mitigates glomerular endothelial permeability and kidney damage through antioxidant, anti‐inflammatory, and KLF4‐dependent mechanisms, offering potential therapeutic benefits for hypertension‐related renal damage.