Azilsartan improves urinary albumin excretion in hypertension mice

Area of Science:

• Nephrology
• Pharmacology
• Cardiovascular Research

Background:

• Hypertension is a primary risk factor for chronic kidney diseases, often leading to hypertensive nephrosclerosis and albuminuria.
• Azilsartan, an angiotensin II type 1 receptor blocker, is used for hypertension, but its specific effects on albuminuria are not well-documented.

Purpose of the Study:

• To investigate the potential renoprotective effects of Azilsartan against albuminuria in a mouse model of hypertension.
• To elucidate the underlying molecular mechanisms, particularly the role of the KLF2/occludin axis, in Azilsartan's action on renal endothelial cells.

Main Methods:

• Utilized a mouse model with angiotensin II and high-salt diet (ANG/HS) to induce hypertensive kidney injury.
• Administered Azilsartan to assess its impact on blood pressure, oxidative stress, inflammation, and urinary albumin excretion.
• Employed human renal glomerular endothelial cells (HrGECs) to evaluate endothelial permeability, occludin and KLF2 expression, and the effect of Azilsartan and KLF2 knockdown.

Main Results:

• Azilsartan dose-dependently reduced blood pressure, oxidative stress, and inflammation in ANG/HS mice.
• Azilsartan treatment reversed ANG/HS-induced increases in urinary albumin excretion and restored occludin expression.
• In HrGECs, Azilsartan prevented increased permeability, reduced occludin and KLF2 expression, and these effects were dependent on KLF2.

Conclusions:

• Azilsartan demonstrates a beneficial effect in mitigating albuminuria associated with hypertension.
• The renoprotective action of Azilsartan involves the KLF2/occludin pathway, highlighting its importance in maintaining endothelial barrier function.
• Azilsartan may represent a therapeutic strategy for managing hypertensive kidney disease by targeting endothelial dysfunction.