Atorvastatin protects endothelium by decreasing asymmetric dimethylarginine in dyslipidemia rats.
BACKGROUND
Asymmetric Dimethylarginine (ADMA) is an inhibitor of endogenous nitric oxide synthase, which is the key synthase for nitric oxide (NO) production. Whether statins could protect endothelium by reducing ADMA concentration is unclear, and whether this effect is associated with the dose of statins usage is also needed further studied.


METHODS
Dyslipidemia rat model was produced by giving high-fat and high-cholesterol diet for 8 weeks. Thereafter, low-dose (5 mg/kg body weight/day) and high-dose (20 mg/kg body weight/day) atorvastatin were orally prescribed for 4 weeks. Parameters of interest including lipid profiles, inflammatory and oxidative markers, NO production and plasma levels of ADMA and ADMA concentration of myocardium were evaluated. Liver enzymes and creatinine kinase (CK) were also detected for safety concern.


RESULTS
At baseline, all parameters were comparable between the sham and the dyslipidemia groups. At 8 weeks of dyslipidemia establishment, as compared to the sham group, body weight and lipid profiles were significantly elevated, and plasma levels of C-reactive protein (CRP), malondialdehyde (MDA) and ADMA were concomitantly increased in accompanying with NO reduction in the dyslipidemia groups. With 4 weeks of atorvastatin therapy, as compared to the control group, lipid disorders and NO production were improved, and plasma levels of CRP, MDA and ADMA were significantly decreased in the high-dose atorvastatin group. ADMA concentration of cardiac tissues was also significantly reduced in the high-dose atorvastatin group. Notably, there was a trend to similar effects which did not reach statistical significance in the low-dose atorvastatin group when compared to the control group. Liver enzyme and CK were comparable after 4 weeks of atorvastatin therapy between groups.


CONCLUSIONS
In rats with dyslipidemia, atorvastatin therapy could reduce plasma level of ADMA and ADMA concentration in cardiac tissues, and these effects are associated with the dose of atorvastatin therapy.
Department of Cardiology, The First Affiliated Hospital of Sun Yat-sen University, 58 Zhongshan Road 2, Guangzhou, 510080, China. zhengyunsen@126.com.
Dongdan
D
Zheng
Department of Emergency Medicine, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510120, China. qingda99@163.com.
Qing
Q
Liang
Department of Cardiology, Shenzhen Sun Yat-sen Cardiovascular Hospital, Shenzhen, 518000, China. zengfanfang@sina.com.
FanFang
F
Zeng
Division of Biomedical Engineering, School of Engineering, Sun Yat-sen University, Guangzhou, 510060, China. maizhch@mail2.sysu.edu.cn.
Zhuocheng
Z
Mai
Department of Cardiology, The First Affiliated Hospital of Sun Yat-sen University, 58 Zhongshan Road 2, Guangzhou, 510080, China. caianping1983@hotmail.com.
Anping
A
Cai
Department of Cardiology, The First Affiliated Hospital of Sun Yat-sen University, 58 Zhongshan Road 2, Guangzhou, 510080, China. qrf168168@163.com.
Ruofeng
R
Qiu
Department of Cardiology, The First Affiliated Hospital of Sun Yat-sen University, 58 Zhongshan Road 2, Guangzhou, 510080, China. xlr168168@163.com.
Rulin
R
Xu
Department of Cardiology, The First Affiliated Hospital of Sun Yat-sen University, 58 Zhongshan Road 2, Guangzhou, 510080, China. ldj168168@yeah.net.
Dongjuan
D
Li
Department of Cardiology, The First Affiliated Hospital of Sun Yat-sen University, 58 Zhongshan Road 2, Guangzhou, 510080, China. wymai@hotmail.com.
Weiyi
W
Mai
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000032:analysis / Q000097:blood; D000069059:Atorvastatin / Q000627:therapeutic use*; D001786:Blood Glucose / Q000032:analysis; D002784:Cholesterol / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood; D003402:Creatine Kinase / Q000097:blood; D050171:Dyslipidemias / Q000188:drug therapy* / Q000503:physiopathology; D004730:Endothelium, Vascular / Q000187:drug effects*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D008297:Male; D009206:Myocardium / Q000737:chemistry; D009569:Nitric Oxide / Q000097:blood; D051381:Rats; D017207:Rats, Sprague-Dawley; D014280:Triglycerides / Q000097:blood
D001786:Blood Glucose; D008076:Cholesterol, HDL; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D014280:Triglycerides; D009569:Nitric Oxide; C018524:N,N-dimethylarginine; D001120:Arginine; D002784:Cholesterol; D000069059:Atorvastatin; D003402:Creatine Kinase