The angiotensin-II receptor antagonist, losartan, inhibits LDL lipid peroxidation and atherosclerosis in apolipoprotein E-deficient mice.
The potential antiatherogenic actions of the angiotensin II receptor antagonist, losartan were investigated in apolipoprotein (apo) E deficient mice, an animal model with severe hypercholesterolemia and extensive atherosclerosis. In these animals accelerated atherosclerosis is associated with increased lipid peroxidation which may play a crucial role in the build up of the atherosclerotic lesions. Administration of losartan (25mg/kg/d) to the apo E deficient mice for a 3-month period increased the plasma renin activity 3.5-fold compared to the placebo group. Losartan increased the resistance of LDL to CuSO4-induced oxidative modification as shown by a significant reduction in the LDL content of malondialdehyde by 55% compared to placebo, as well as by the prolongation of the lag time required for LDL oxidation, from 60 min in the placebo-treated mice to more than 140 min in the losartan-treated mice. Losartan reduced significantly the mean atherosclerotic lesion area by 80% compared to the placebo group. We conclude that losartan inhibits LDL lipid peroxidation in the apo E deficient mice and this effect may have an important role in the attenuation of the accelerated atherosclerosis.
Keidar
S
S
The Lipid Research Laboratory, Rambam Medical Center, Technion Faculty of Medicine and the Rappaport Institute for Research in the Medical Sciences, Haifa, Israel. skeidar@rambam.health.gov.il
Attias
J
J
Smith
J
J
Breslow
J L
JL
Hayek
T
T
D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency*; D001161:Arteriosclerosis / Q000209:etiology / Q000517:prevention & control*; D001713:Biphenyl Compounds / Q000494:pharmacology* / Q000627:therapeutic use; D019327:Copper Sulfate / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology* / Q000627:therapeutic use; D015227:Lipid Peroxidation / Q000187:drug effects*; D008077:Lipoproteins, LDL / Q000378:metabolism*; D019808:Losartan; D008315:Malondialdehyde / Q000378:metabolism; D051379:Mice; D008817:Mice, Mutant Strains; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D012083:Renin / Q000097:blood; D013777:Tetrazoles / Q000494:pharmacology* / Q000627:therapeutic use
D057911:Angiotensin Receptor Antagonists; D001057:Apolipoproteins E; D001713:Biphenyl Compounds; D007093:Imidazoles; D008077:Lipoproteins, LDL; D013777:Tetrazoles; D008315:Malondialdehyde; D012083:Renin; D019808:Losartan; D019327:Copper Sulfate