期刊
HYPERTENSION
卷 44, 期 5, 页码 758-763出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/01.HYP.0000145179.44166.0f
关键词
angiotensin; atherosclerosis; oxidative stress
We investigated the effects of a 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor ( statin) on the inhibitory effects of an angiotensin II type-1 receptor (AT(1)) blocker on atherosclerosis and explored cellular mechanisms. We gave apolipoprotein E null mice a high-cholesterol diet for 10 weeks and measured atherosclerotic plaque area and lipid deposition. Neither 1 mg/kg per day of valsartan nor 3 mg/kg per day of fluvastatin had any effect on blood pressure or cholesterol concentration; however, both drugs decreased plaque area and lipid deposition after 10 weeks. We then reduced the doses of both drugs to 0.1 mg/kg per day and 1 mg/kg per day, respectively. At these doses, neither drug had an effect on atherosclerotic lesions. When both drugs were combined at these doses, a significant reduction in atherosclerotic lesions was observed. Similar inhibitory effects of valsartan or fluvastatin on the expressions of nicotinamide-adenine dinucleotide/nicotinamide-adenine dinucleotide phosphate oxidase subunits p22(phox) and p47(phox), production of superoxide anion, the expression of monocyte chemoattractant protein-1, and intercellular adhesion molecule-1 expression were observed. These results suggest that concomitant AT(1) receptor and cholesterol biosynthesis blockade, particularly when given concomitantly, blunts oxidative stress and inflammation independent of blood pressure or cholesterol-related effects.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据