Effects of simvastatin on activities of endogenous antioxidant enzymes and angiotensin-converting enzyme in rat myocardium with pressure-overload cardiac hypertrophy.
OBJECTIVE
To investigate effects of simvastatin (Sim) on the activities of antioxidant enzymes and angiotensin-converting enzyme in rat myocardium with pressure-overload cardiac hypertrophy.


METHODS
Left ventricular hypertrophy (LVH) was induced by partly constricting rat abdominal aorta between the left and right renal artery. Rats were given ig Sim 1.8 and 3.6 mg . kg-1 . d-1 for 8 weeks following 6 weeks aortic constriction. Activities of antioxidant enzymes and angiotensin-converting enzyme, and lipid peroxidation of left ventricular (LV) tissue were determined.


RESULTS
Contents of angiotensin II and thiobarbituric acid reactive substances (TBARS), and activity of ACE in LVH group (n = 8) were increased by 163 %, 90 %, and 130 %, respectively (P < 0.01)compared with sham-operated group (n = 7), and were decreased by 30 %, 37 %, and 51 %, respectively (P < 0.01) in high dosage Sim treatment group (n = 9) compared with LVH group. Activities of catalase and glutathione peroxidase of LV tissue in LVH group were decreased by 29 % and 23 % (P < 0.01) compared with sham-operated group, and were increased by 32 % and 22 % (P < 0.01) in high dosage Sim treatment group compared with LVH group. Activity of Cu, Zn-superoxide dismutase (SOD) of LV tissue was increased by 33 % in LVH group compared with sham-operated group. Sim treatment did not significantly affect activity of Cu,Zn-SOD.


CONCLUSIONS
Alteration of redox status in myocardium is associated with cardiac hypertrophy and inhibitory effects of Sim on cardiac hypertrophy in rats model might be linked to its antioxidant effects.
Luo
Jian-Dong
JD
Department of Pharmacology, Guangzhou Medical College, Guangzhou 510182, China. joluoa@public.guangzhou.gd.cn
Zhang
Wei-Wen
WW
Zhang
Gui-Ping
GP
Zhong
Bei-Hua
BH
Ou
Hui-Jian
HJ
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001013:Aorta, Thoracic / Q000473:pathology; D002374:Catalase / Q000378:metabolism; D003250:Constriction; D005979:Glutathione Peroxidase / Q000378:metabolism; D006321:Heart / Q000187:drug effects*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology; D017379:Hypertrophy, Left Ventricular / Q000473:pathology*; D008297:Male; D009206:Myocardium / Q000201:enzymology*; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D019821:Simvastatin / Q000494:pharmacology*; D013482:Superoxide Dismutase / Q000378:metabolism*
D000975:Antioxidants; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D017382:Reactive Oxygen Species; D019821:Simvastatin; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D007703:Peptidyl-Dipeptidase A