Doxazosin and cholestyramine similarly decrease fatty streak formation in the aortic arch of hyperlipidemic hamsters.

Area of Science:

• Pharmacology
• Cardiovascular Research
• Atherosclerosis Research

Background:

• Atherosclerosis is a complex disease driven by lipid accumulation and inflammation.
• Hyperlipidemia is a major risk factor for atherosclerosis development.
• Alpha-1 adrenergic inhibitors are used to manage hypertension, but their role in atherosclerosis is less understood.

Purpose of the Study:

• To investigate the effects of doxazosin on atherosclerosis in a hyperlipidemic hamster model.
• To compare the efficacy of doxazosin with cholestyramine, a known lipid-lowering agent, in reducing atherosclerotic markers.

Main Methods:

• Hyperlipidemic hamsters were treated with doxazosin or cholestyramine for 8 weeks.
• Plasma lipids, mean arterial pressure (MAP), and heart rate (HR) were monitored.
• Aortic arch analysis included foam cell quantification, size, and lipid accumulation (Oil red O staining).

Main Results:

• Doxazosin and cholestyramine significantly reduced plasma total cholesterol, LDL+VLDL cholesterol, and triglycerides.
• Doxazosin decreased MAP by 18% without affecting HR.
• Both treatments reduced foam cell number, size, and lipid accumulation in the aortic arch.

Conclusions:

• Doxazosin effectively decreases plasma lipids and inhibits the development of fatty streaks in hyperlipidemic hamsters.
• The anti-atherosclerotic effect of doxazosin was comparable to that of cholestyramine.
• Doxazosin demonstrates potential as a therapeutic agent for managing atherosclerosis, particularly in lipid-driven disease contexts.