title: Doxazosin, an alpha-1 antagonist, prevents further progression of the advanced atherosclerotic lesion in hypercholesterolemic hamsters.
abstract: 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.
authors.affiliation: Center for Health and Disease Research, Division of Nutrition and Metabolic Disorders, Univeristy of Massachusetts Lowell, Lowell, MA 01854, USA.
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Wilson
authors.forename: Thomas L
authors.initials: TL
authors.lastname: Foxall
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Nicolosi
mesh_terms: D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000818:Animals; D000924:Anticholesteremic Agents / Q000494:pharmacology*; D001011:Aorta / Q000473:pathology; D001161:Arteriosclerosis / Q000097:blood / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D002784:Cholesterol / Q000097:blood*; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D006224:Cricetinae; D017292:Doxazosin / Q000008:administration & dosage / Q000494:pharmacology*; D006937:Hypercholesterolemia / Q000097:blood / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008647:Mesocricetus; D013997:Time Factors; D014280:Triglycerides / Q000097:blood
chemical_list: D000317:Adrenergic alpha-Antagonists; D000924:Anticholesteremic Agents; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D014280:Triglycerides; D002784:Cholesterol; D017292:Doxazosin