Doxazosin, an alpha-1 antagonist, prevents further progression of the advanced atherosclerotic lesion in hypercholesterolemic hamsters.

The aim of this study was to examine the effect of doxazosin (DOX) on the further progression and regression of the advanced atherosclerotic lesion in the hypercholesterolemic hamster. Thirty-six, male F(1)B Golden Syrian hamsters, 10 weeks of age, were divided into 3 groups of 12 and fed a nonpurified hypercholesterolemic diet (HCD) containing 10% coconut oil and 0.1% cholesterol (wt/wt) for 9 months (HCD 9). One group of hamsters was euthanized at 9 months and their aortas were collected, fixed, and stored until analysis. The remaining hamsters were either maintained on the HCD for an additional 6 months (HCD 15) or fed the HCD plus 20 mg/kg/d DOX for the 6 months. At the end of the study (15 months), the DOX-treated hamsters had significantly lower plasma total cholesterol (TC) (-68%), low-density lipoprotein-cholesterol (LDL-C) (-73%), and triglycerides (TG) (-74%) compared with the HCD 15. The lumenal narrowing and intimal thickening atherosclerotic lesions were significantly less in the DOX-treated hamsters compared with the HCD 15 (-66% and -70%, respectively). These data suggest that DOX treatment prevents further progression of the advanced atherosclerotic lesion possibly by lowering plasma TC, LDL-C, and TG in hypercholesterolemic hamsters.