Simvastatin treatment restores vasoconstriction and the inhibitory effect of LPC on endothelial relaxation via affecting oxidizing metabolism in diabetic rats.
Oxidative stress and dyslipidaemia play an important role in the development of diabetes-induced vascular complications. The aim of this study was to examine the reversal effects of simvastatin on some metabolic and oxidative parameters, and vascular functions in diabetic rats. Diabetes was induced by a single injection of streptozotocin (STZ, 45 mg/kg, i.p.). Eight weeks after STZ induction, some of the diabetic and control rats were treated with simvastatin (10 mg/kg rat/d) for 4 weeks. Plasma glucose, triglyceride and total cholesterol concentrations were significantly increased in 12-week diabetic rats. Simvastatin treatment stopped the loss of body weight, completely normalized the increase of plasma lipids and partially reduced the hyperglycaemia in diabetic rats. Increased malondialdehyde levels, catalase and glutathione peroxidase activities were normalised by simvastatin treatment in diabetic aorta. Phenylephrine (PE)-induced contractility in aorta rings was unaffected by diabetes, but was markedly decreased after simvastatin treatment in both control and diabetic rats. Reduction of endothelium-dependent vasorelaxation in diabetes was significantly ameliorated by simvastatin treatment. Incubation of aorta rings with lysophosphatidylcholine, a component of the oxidized LDL, did not significantly affect PE-induced contractions, but reduced endothelium-dependent relaxations more in untreated-diabetic rats than in other experimental groups. The endothelium-independent vasorelaxations were similar in all ring preparations. These results indicate that simvastatin treatment may ameliorate diabetes-induced abnormal vasoconstriction and endothelial dysfunction via affecting general and oxidizing metabolism, nitric oxide disability and intracellular calcium mobilisation.
Ceylan
A
A
Department of Pharmacology, Faculty of Pharmacy, Ankara University, Ankara, Turkey.
Karasu
C
C
Aktan
F
F
Ozansoy
G
G
D000818:Animals; D001011:Aorta / Q000187:drug effects; D001786:Blood Glucose / Q000032:analysis; D001835:Body Weight / Q000187:drug effects; D002784:Cholesterol / Q000097:blood; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000187:drug effects*; D000960:Hypolipidemic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D019821:Simvastatin / Q000494:pharmacology / Q000627:therapeutic use*; D013311:Streptozocin / Q000633:toxicity; D014280:Triglycerides / Q000097:blood; D014664:Vasodilation / Q000187:drug effects
D001786:Blood Glucose; D000960:Hypolipidemic Agents; D014280:Triglycerides; D013311:Streptozocin; D002784:Cholesterol; D019821:Simvastatin