This Article Order Full text via Infotrieve Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Foxall, T. L. Articles by Wong, S. S. Search for Related Content PubMed PubMed Citation Articles by Foxall, T. L. Articles by Wong, S. S.

American Journal of Pathology, Vol 140, 1357-1363, Copyright © 1992 by American Society for Investigative Pathology

REGULAR ARTICLES

Dose-related effects of doxazosin on plasma lipids and aortic fatty streak formation in the hypercholesterolemic hamster model

TL Foxall, GT Shwaery, AF Stucchi, RJ Nicolosi and SS Wong
Department of Animal and Nutritional Sciences, University of New Hampshire, Durham.

Doxazosin, an alpha 1-adrenergic inhibitor, has been shown to decrease hypertension and plasma lipids, especially total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C), thus reducing certain risk factors associated with increased incidence of cardiovascular disease. One preliminary report indicated that the decrease in LDL-C in hypercholesterolemic hamsters treated with doxazosin was associated with a reduction in fatty streak formation. However, since the effects of doxazosin on plasma lipids, aortic fatty streak development, or the relationship between the two have not been studied in a dose-dependent manner, these effects were further investigated over varying doses of doxazosin (0, 1, 5, 10, and 20 mg/kg body wt/day) during a 10-week period. Doxazosin administration was associated with a dose-dependent decrease in LDL-C of 2%, 29%, 52%, and 60%, whereas the degree of fatty streak formation was reduced 11%, 45%, 76%, and 92% compared with controls, with the first statistically significant decrease for both parameters at the 10 mg/kg dose. Significant correlations between LDL-C concentrations and fatty streak area suggest that doxazosin altered aortic lipid infiltration primarily by its effect on plasma lipids. However, the 20 mg/kg dose of doxazosin significantly decreased lesion area compared with the 10 mg/kg dose without a further effect on plasma lipid concentrations. Three animals at these higher doses demonstrated no stainable lipid inclusions while maintaining plasma lipid values similar to their cohorts. These exceptions to the lipid-lesion relationship raise the possibility of additional effects of doxazosin, which may occur independent of or in concert with lipoprotein cholesterol lowering, on lesion formation.

This article has been cited by other articles:

				S. E. Dorfman, D. E. Smith, D. P. Osgood, and A. H. Lichtenstein Study of Diet-Induced Changes in Lipoprotein Metabolism in Two Strains of Golden-Syrian Hamsters J. Nutr., December 1, 2003; 133(12): 4183 - 4188. [Abstract] [Full Text] [PDF]

				A. Matsuda, Y. Suzuki, K. Kondo, Y. Ikeda, and K. Umemura Hypercholesterolemia induces regression in neointimal thickening due to apoptosis of vascular smooth muscle cells in the hamster endothelial injury model Cardiovasc Res, February 1, 2002; 53(2): 512 - 523. [Abstract] [Full Text] [PDF]

				R. J. Nicolosi, T. A. Wilson, E. J. Rogers, and D. Kritchevsky Effects of specific fatty acids (8:0,14:0, cis-18:1, trans-18:1) on plasma lipoproteins, early atherogenic potential, and LDL oxidative properties in the hamster J. Lipid Res., October 1, 1998; 39(10): 1972 - 1980. [Abstract] [Full Text]

				A. J. Dabbagh, G. T. Shwaery, J. F. Keaney Jr, and B. Frei Effect of Iron Overload and Iron Deficiency on Atherosclerosis in the Hypercholesterolemic Rabbit Arterioscler. Thromb. Vasc. Biol., November 1, 1997; 17(11): 2638 - 2645. [Abstract] [Full Text]