Protective effects of lovastatin on vascular endothelium injured by low density lipoprotein

Feng-Xia Ma, Li-Ying Liu, Xiao-Ming Xiong
Acta Pharmacologica Sinica 2003, 24 (10): 1027-32

AIM: To examine protective effects of lovastatin, an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, on endothelial dysfunction induced by a single intravenous injection of natural low density lipoprotein (n-LDL) and analyze the possible action mechanism of lovastatin.

METHODS: Rats were treated by intraperitoneal injection with lovastatin at dose of 2 or 4 mg/kg body weight once daily for 7 d, and on d 6 a single injection of n-LDL 4 mg/kg was given by sublingual vein. Forty eight hours after injection of n-LDL, the descending thoracic aorta of rats was taken. Acetylcholine (ACh)-induced endothelium-dependent relaxation (EDR) and sodium nitroprusside (SNP)-induced endothelium-independent relaxation of aortic rings were examined in vitro. Malondialdehyde (MDA), nitric oxide (NO), and activity of superoxide dismutase (SOD) as well as level of lipid in serum were analyzed.

RESULTS: A single injection of n-LDL inhibited ACh-induced EDR compared with normal control group (maximal relaxation rate: 69.5 %+/-1.2 % vs 91.0 %+/-1.2 %, P<0.05), decreased serum NO level [(7.0+/-0.5) micromol/L vs (11.2+/-0.9) micromol/L, P<0.05] and serum SOD activity [(371+/-16) kNU/L vs (405+/-18) kNU/L, P<0.05] and elevated serum MDA level [(5.4+/-0.5) micromol/L vs (3.0+/-0.8) micromol/L, P<0.05]. Compared with n-LDL treated group, lovastatin 2 and 4 mg/kg increased EDR( maximal relaxation rate 82.9 %+/-0.5% and 83.7 %+/-0.7 % vs 69.5 %+/-1.2 %, P<0.05) and elevated NO level [(11.0+/-0.7) and (11.2+/-0.8) micromol/L vs (7.0+/-0.5) micromol/L, P<0.05], increased SOD activity [(402+/-15) and (408+/-25) kNU/L vs (371+/-16) kNU/L, P<0.05], and reduced serum MDA level [(3.3+/-0.6) and (3.5+/-0.4) micromol/L vs (5.4+/-0.5) micromol/L, P<0.05]. But sodium nitroprusside-induced endothelium-independent relaxation and the level of serum lipid in both saline+LDL group and lovastatin-treated group had no marked alteration.

CONCLUSION: Lovastatin was able to protect vascular endothelium from dysfunction induced by a single injection of n-LDL.

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