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Effect of doxazosin on plasma lipids and atherogenesis: a preliminary report.

Abstract
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.
AuthorsM C Kowala, R J Nicolosi
JournalJournal of cardiovascular pharmacology (J Cardiovasc Pharmacol) Vol. 13 Suppl 2 Pg. S45-9; discussion S49 ( 1989) ISSN: 0160-2446 [Print] United States
PMID2471015 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Adrenergic alpha-Antagonists
  • Cholesterol, HDL
  • Cholesterol, LDL
  • Triglycerides
  • Cholesterol
  • Doxazosin
  • Prazosin
Topics
  • Adrenergic alpha-Antagonists (pharmacology)
  • Animals
  • Arteriosclerosis (etiology)
  • Blood Pressure (drug effects)
  • Cholesterol (blood)
  • Cholesterol, HDL (blood)
  • Cholesterol, LDL (blood)
  • Doxazosin
  • Female
  • Foam Cells (drug effects)
  • Gerbillinae (metabolism)
  • Heart Rate (drug effects)
  • Male
  • Prazosin (analogs & derivatives, pharmacology)
  • Triglycerides (blood)

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