Tissue-specific effects of atorvastatin on 3-hydroxy-3-methylglutarylcoenzyme A reductase expression and activity in spontaneously hypertensive rats.
OBJECTIVE
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 HMGCoA 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.


CONCLUSIONS
The present study demonstrates that the effects of atorvastatin on tissue cholesterol content and HMG-CoA reductase are strain- and tissue-specific.
Chen
Guo-ping
GP
Institute of Cardiology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, China.
Yao
Lei
L
Lu
Xian
X
Li
Liang
L
Hu
Shen-jiang
SJ
D000818:Animals; D000069059:Atorvastatin; D002784:Cholesterol / Q000097:blood; D002851:Chromatography, High Pressure Liquid; D006538:Heptanoic Acids / Q000494:pharmacology*; D006903:Hydroxymethylglutaryl CoA Reductases / Q000096:biosynthesis*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D007668:Kidney / Q000187:drug effects / Q000201:enzymology; D050356:Lipid Metabolism / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000201:enzymology; D009206:Myocardium / Q000201:enzymology; D011758:Pyrroles / Q000494:pharmacology*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY
D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011758:Pyrroles; D002784:Cholesterol; D000069059:Atorvastatin; D006903:Hydroxymethylglutaryl CoA Reductases