Tissue-specific effects of atorvastatin on 3-hydroxy-3-methylglutaryl-coenzyme A reductase expression and activity in spontaneously hypertensive rats  

作　　者：Guo-ping CHEN Lei YAO Xian LU Liang LI Shen-jiang HU 

机构地区：[1]Institute of Cardiology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003. China [2]Division of Nitric Oxide and Inflammatory Medicine. E-Institute of Shanghai Universities, Shanghai 201203, China

出　　处：《Acta Pharmacologica Sinica》2008年第10期1181-1186,共6页中国药理学报（英文版）

摘　　要：Aim： Cardiovascular remodeling is closely associated with cholesterol and is attenuated by statins. The spontaneously hypertensive rat （SHR） has a low serum cholesterol level and evident cardiovascular remodeling. The aims of the present study were to characterize the effects of atorvastatin on tissue cholesterol content and 3-hydroxy-3-methylglutaryl-coenzyme A （HMG-CoA） reductase expression and activity in four tissues from SHR： liver, heart, aorta and kidney. Methods： SHR and normotensive Wistar-Kyoto rats （WKY） were treated daily with atorvastatin （50 mg/kg） for 8 weeks. Cholesterol levels of serum and tissues （liver, heart, aorta and kidney） were determined by commercial enzymatic methods. Western blot analysis and high performance liquid chromatogram （HPLC） were used to assay the expression and activity of enzyme respectively. Results： Treatment with atorvastatin decreased cholesterol content and HMG- CoA reductase expression and activity in all four tissues of SHR. However, in WKY, atorvastatin only altered HMG-CoA reductase in liver, where the protein expression was upregulated but the enzyme activity was decreased. Conclusion： The present study demonstrates that the effects of atorvastatin on tissue cholesterol content and HMG-CoA reductase are strain- and tissue-specific.Aim： Cardiovascular remodeling is closely associated with cholesterol and is attenuated by statins. The spontaneously hypertensive rat （SHR） has a low serum cholesterol level and evident cardiovascular remodeling. The aims of the present study were to characterize the effects of atorvastatin on tissue cholesterol content and 3-hydroxy-3-methylglutaryl-coenzyme A （HMG-CoA） reductase expression and activity in four tissues from SHR： liver, heart, aorta and kidney. Methods： SHR and normotensive Wistar-Kyoto rats （WKY） were treated daily with atorvastatin （50 mg/kg） for 8 weeks. Cholesterol levels of serum and tissues （liver, heart, aorta and kidney） were determined by commercial enzymatic methods. Western blot analysis and high performance liquid chromatogram （HPLC） were used to assay the expression and activity of enzyme respectively. Results： Treatment with atorvastatin decreased cholesterol content and HMG- CoA reductase expression and activity in all four tissues of SHR. However, in WKY, atorvastatin only altered HMG-CoA reductase in liver, where the protein expression was upregulated but the enzyme activity was decreased. Conclusion： The present study demonstrates that the effects of atorvastatin on tissue cholesterol content and HMG-CoA reductase are strain- and tissue-specific.

关 键 词：HMG-CoA reductase ATORVASTATIN spontaneously hypertensive rat 

分 类 号：R97[医药卫生—药品]