Aspirin Protected Against Endothelial Damage Induced by LDL: Role of Endogenous NO Synthase Inhibitors in Rats
Sheng Deng；Pan-Yue Deng；Jun-Lin Jiang；Feng Ye；Jing Yu；Tian-Lun Yang；Han-Wu Deng；Yuan-Jian Li
aspiri ； low-density lipoprotein ； asymmetric dimethylarginine ； dimethylaminohydrolase ； endothelium
Acta Pharmacologica Sinica
|Volume or Term/Year and Month of Publication||
25卷12期（2004 / 12 / 01）
1633 - 1639
AIM: To study the protective effect of aspirin on damages of the endothelium induced by low-density lipoprotein (LDL), and whether the protective effect of aspirin is related to reduction of nitric oxide synthase inhibitor level. METHODS: Vascular endothelial injury was induced by a single injection of native LDL (4 mg/kg) in rats. Vasodilator responses to acetylcholine (ACh) in the isolated aortic rings were determined, and serum concentrations of asymmetric dimethylarginine (ADMA), malondialdehyde (MDA), tumour necrosis factor-α (TNF-α), and the activity of dimethylaminohydrolase (DDAH) were measured. RESULTS: A single injection of LDL (4 mg/kg) significantly decreased vasodilator responses to ACh, increased the serum level of ADMA, MDA, and TNF-α, and decreased DDAH activity. Aspirin (30 or 100 mg/kg) markedly reduced the inhibition of vasodilator responses to ACh by LDL, and the protective effect of aspirin at the lower dose was greater compared with high-dose aspirin group. Aspirin inhibited the increased level of MDA and TNF-α induced by LDL. Aspirin at the dose of 30 mg/kg, but not at higher dose (100 mg/kg), significantly reduced the concentration of ADMA and increased the activity of DDAH. CONCLUSION: Aspirin at the lower dose (30 mg/kg) protects the endothelium against damages elicited by LDL in vivo, and the protective effect of aspirin on endothelium is related to reduction of ADMA concentration by increasing DDAH activity.