Amlodipine improves aortic dysfunction in atherosclerotic mice

Area of Science:

• Cardiovascular Research
• Pharmacology
• Vascular Biology

Background:

• Calcium channel blockers are used for hypertension and arrhythmias.
• Amlodipine (AMLO) has potential anti-atherosclerotic effects, but its impact on vascular function requires further investigation.
• Existing studies often focus on histological and biochemical markers, lacking functional assessments.

Purpose of the Study:

• To test the hypothesis that amlodipine improves vascular function in atherosclerosis.
• To assess the effects of amlodipine on pulse wave velocity (PWV) and cortical stiffness in an atherosclerosis mouse model.
• To explore the mechanism underlying amlodipine's vascular effects.

Main Methods:

• Atherosclerosis was induced in C57BL/6N mice using PCSK9(DY) injection and a Western diet (WD).
• Mice were treated with amlodipine (AMLO) or vehicle (VEH).
• Vascular function was assessed via in vivo pulse wave velocity (PWV) measurement and ex vivo/in vitro cortical stiffness determination.

Main Results:

• Amlodipine treatment reduced plaque burden, calcification, and increased nitric oxide (NO) levels in atherosclerotic mice.
• AMLO normalized elevated PWV and cortical stiffness in atherosclerotic mice.
• AMLO also improved vascular function and glycocalyx height in non-atherosclerotic control mice, indicating an atherosclerosis-independent effect.

Conclusions:

• Amlodipine (AMLO) effectively improves vascular function in atherosclerosis by normalizing pulse wave velocity and cortical stiffness.
• The beneficial effects of AMLO on vascular function are independent of atherosclerosis development.
• The mechanism of action appears to be nitric oxide (NO)-dependent.