Effect of doxazosin on plasma lipids and atherogenesis: a preliminary report.
Chronic treatment with selective alpha 1-inhibitors has a beneficial impact on plasma lipids and arterial pressure. To study the effect of selective alpha 1-inhibition on atherogenesis, gerbils and hamsters were fed rodent chow containing 0.2% cholesterol and 10% coconut oil (by weight). One group of each species received the selective alpha 1-inhibitor doxazosin (gerbil, 17 mg/kg/day; hamster, 11 mg/kg/day) in the diet. In gerbils treated for 6 weeks with doxazosin, plasma total cholesterol fell by 39% and very-low-density lipoprotein (VLDL) plus low-density lipoprotein (LDL) cholesterol by 52% compared with control levels. Plasma triglyceride and high-density lipoprotein (HDL) cholesterol were unaffected. In hamsters treated with doxazosin for 6 weeks, plasma total cholesterol, VLDL plus LDL cholesterols, and triglyceride were reduced by approximately 40% compared with hyperlipidemic controls. HDL cholesterol, mean arterial pressure, and heart rate were not significantly altered. Using en face preparations of the hamster aortic arch, intimal macrophage-derived foam cells were quantitated. Compared with controls, doxazosin reduced the number of intimal foam cells/mm2 by 71%. We suggest that selective alpha 1-inhibition reduces foam cell accumulation by lowering plasma lipids and/or by a direct effect on the arterial wall.
Kowala
M C
MC
Department of Clinical Sciences, University of Lowell, Massachusetts 01854.
Nicolosi
R J
RJ
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000818:Animals; D001161:Arteriosclerosis / Q000209:etiology*; D001794:Blood Pressure / Q000187:drug effects; D002784:Cholesterol / Q000097:blood*; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D017292:Doxazosin; D005260:Female; D005487:Foam Cells / Q000187:drug effects; D005849:Gerbillinae / Q000378:metabolism; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D011224:Prazosin / Q000031:analogs & derivatives* / Q000494:pharmacology; D014280:Triglycerides / Q000097:blood*
D000317:Adrenergic alpha-Antagonists; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D014280:Triglycerides; D002784:Cholesterol; D017292:Doxazosin; D011224:Prazosin