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

Key Words

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)

Page #

1633 - 1639

Content Language


English Abstract

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.

Topic Category 醫藥衛生 > 藥理醫學