Protective Effects Of Lovastatin On Vascular Endothelial Function Injured By Low Density Lipoprptein

Aim: To examine protective effects of lovastatin on endothelial dysfunction induced by natural low density lipoprotein (n-LDL) and analyze the possible mechanism of lovastatin.Methods: 48 healthy male sprague-dawley rats were divided randomly to 6 groups with 8 rats in each group. ① normal control group; ②n-LDL-injured group; ③low dose(2mg/kg) and high dose(4mg/kg) of lovastatin-treated group; ④ solvent control group; ⑤ L-NNA+lovastatin-treated group. Rats of lovastatin-treated group were intraperitonealy injected with lovastatin once daily for 7d. And rats of L-NNA+lovastatin-treated group were intraperitonealy injected with L-NNA at dose of 20 mg/kg daily for 3 d in the first three day of lovastatin injection. Rats of other groups were intraperitonealy injected with solvent or saline 2 ml/kg. Except normal control group, on the sixth day of lovastatin injection, rats were given a single injection of n-LDL( 4mg/kg )in the sublingual vein.48 h after injection of n-LDL, rats were anesthetized with sodium pentobarbital, and blood samples were collected from carotid artery, concentration of MDA, NO and activity of SOD as well as level of lipid in serum were analyzed, the thoracic aorta of rats was taken, andACh-induced EDR and SNP-induced endothelium-independent relaxation of aortic rings were examined.Results: A single injection of n-LDL(4mg/kg) significantly inhibited ACh-induced EDR, decreased concentration of serum NO, activity of serum SOD and elevated serum MDA level, but had no effect on SNP-induced endothelial-independent relaxation and serum lipid level, lovastatin at both doses of 2 and 4 mg/kg markedly attenuated n-LDL-induced inhibition of EDR , increase of serum MDA level , reduction of both NO concentration and activity of SOD in serum. Protective effects of lovastatin on vascular endothelial function were reversed by L-NNA.Conclusion: A single intravenous injection of n-LDL(4mg/kg) induced vascular endothelial dysfunction, lovastatin protected against vascular endothelial dysfunction induced by n-LDL. The mechanism of lovastatin was related to enhance NO pathway and inhibit oxidative stress.