Aspirin protected against endothelial damage induced by LDL: role of endogenous NO synthase inhibitors in rats.
OBJECTIVE
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-alpha (TNF-alpha), 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-alpha, 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-alpha 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.


CONCLUSIONS
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.
Deng
Sheng
S
Department of Pharmacology, School of Pharmaceutical Science, Central South University, Changsha 410078, China.
Deng
Pan-yue
PY
Jiang
Jun-lin
JL
Ye
Feng
F
Yu
Jing
J
Yang
Tian-lun
TL
Deng
Han-du
HD
Li
Yuan-jian
YJ
D000581:Amidohydrolases / Q000378:metabolism; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D001120:Arginine / Q000031:analogs & derivatives* / Q000097:blood*; D001241:Aspirin / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000037:antagonists & inhibitors*; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D009119:Muscle Contraction / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D008077:Lipoproteins, LDL; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D008315:Malondialdehyde; C018524:N,N-dimethylarginine; D001120:Arginine; D019001:Nitric Oxide Synthase; D000581:Amidohydrolases; C059999:dimethylargininase; D001241:Aspirin