Effect of fenofibrate on LDL-induced endothelial dysfunction in rats.
Previous investigations have demonstrated that asymmetric dimethylarginine (ADMA) is an important factor contributing to endothelial dysfunction, and that fenofibrate has a protective effect on the endothelium in hyperlipidaemic patients. In the present study in rats treated with native low-density lipoprotein (nLDL), we addressed the question of whether the beneficial effect of fenofibrate on endothelial cells is related to reduction of the ADMA concentration. A single injection of nLDL (4 mg/kg, 48 h) markedly reduced endothelium-dependent relaxation in response to acetylcholine and the plasma level of nitrite/nitrate and increased the plasma concentrations of ADMA, malonyldialdehyde (MDA) and tumour necrosis factor-alpha (TNF-alpha). Treatment with fenofibrate (30 or 100 mg/kg) significantly reduced the inhibition of vasodilator responses to acetylcholine, decreased the elevated levels of ADMA, MDA and TNF-alpha, and enhanced the decreased level of nitrite/nitrate in the rats treated with LDL. These results suggest that the protective effect of fenofibrate on endothelial cells in rats treated with LDL may be related to the reduction of ADMA concentration.
Department of Cardiovascular Medicine, Xiang-Ya Hospital, Central South University, Changsha, Hunan 410008, China.
Tian-Lun
TL
Yang
Mei-Fang
MF
Chen
Bai-Ling
BL
Luo
Jing
J
Yu
Jun-Lin
JL
Jiang
Yuan-Jian
YJ
Li
D000109:Acetylcholine; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001013:Aorta, Thoracic / Q000187:drug effects / Q000502:physiology; D001120:Arginine / Q000031:analogs & derivatives* / Q000097:blood; D003404:Creatinine / Q000097:blood; D004730:Endothelium, Vascular / Q000378:metabolism* / Q000502:physiology; D011345:Fenofibrate / Q000494:pharmacology*; D000960:Hypolipidemic Agents / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology; D009566:Nitrates / Q000097:blood; D009573:Nitrites / Q000097:blood; D010656:Phenylephrine; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014664:Vasodilation / Q000187:drug effects
D000893:Anti-Inflammatory Agents; D000960:Hypolipidemic Agents; D009566:Nitrates; D009573:Nitrites; D014409:Tumor Necrosis Factor-alpha; C487735:dimethylarginine; D010656:Phenylephrine; D008315:Malondialdehyde; D001120:Arginine; D003404:Creatinine; D000109:Acetylcholine; D011345:Fenofibrate