[Protective effects of metformin on low-density lipoprotein-induced endothelial dysfunction in rats].
OBJECTIVE
To observe the protective effect of metformin on the endothelial function and the mechanisms in rats with low-density lipoprotein (LDL) injection.


METHODS
A single dose (4 mg/kg) of natural LDL was injected through the sublingual vein of rats to induce vascular endothelial dysfunction. Blood samples were then collected from the rats to detect the concentrations of malondialdehyde (MDA) and nitric oxide (NO), activity of superoxide dismutase (SOD) and serum lipid levels. The thoracic aorta of rats was obtained to assay acetylcholine (ACh)-induced endothelium-dependent relaxation (EDR) and sodium nitroprusside (SNP)-induced endothelium-independent relaxation. The effects of metformin pretreatment on the endothelial functions in the rats were investigated.


RESULTS
A single-dose LDL significantly inhibited ACh-induced EDR without affecting SNP-induced endothelial-independent relaxation. The injection decreased serum NO and elevated serum MDA level, but had no effect on serum lipid level. Metformin markedly attenuated LDL-induced inhibition of EDR, serum MDA elevation, and serum NO reduction without affecting the serum lipid levels.


CONCLUSIONS
Metformin provides protection against vascular endothelial dysfunction induced by LDL in rats, the mechanism of which is probably associated with protection of endothelium-dependent relaxation factor and inhibition of the oxidative stress.
Xie
Wei
W
Department of Cardiology, Xiangya Hospital, Central South University, Changsha 410008, China.
Zhang
Sai-dan
SD
Ou
Xi-ping
XP
Yang
Tian-lun
TL
D000818:Animals; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology*; D045462:Endothelium-Dependent Relaxing Factors / Q000378:metabolism*; D008077:Lipoproteins, LDL / Q000008:administration & dosage*; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D008687:Metformin / Q000494:pharmacology*; D009569:Nitric Oxide / Q000097:blood; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000378:metabolism; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*
D045462:Endothelium-Dependent Relaxing Factors; D008077:Lipoproteins, LDL; D009569:Nitric Oxide; D008315:Malondialdehyde; D008687:Metformin; D013482:Superoxide Dismutase