Eugenosedin-A (Eu-A) effects on vascular endothelial dysfunction and oxidativestress in a hyperlipidemic rat model were investigated. Rats were randomly divided into fourgroups: two control groups and two treatment groups. The control rats received a regular dietor high fat diet (HFD); the treatment rats fed received an HFD with 5 mg/kg Eu-A or atorvastatinfor 10 weeks. No changes in serotonin levels were observed in the four groups; norepinephrinelevels were enhanced in the HFD group which was attenuated by Eu-A andatorvastatin. In the HFD group, the vascular reactivity was increased by vasoconstrictors (5-nonyloxytryptamine, 5-HT, and phenylephrine) and decreased by an endothelium-dependentvasorelaxant, carbachol. Protein levels of a1-adrenergic receptors (not 5-HT1B/2A), reactive oxygenspecies (ROS) p47phox, p67phox, and gp91phox, and oxidative damage markers 3-nitrotyrosine (3-NT) and 4-hydroxy-2-nonenal (4-HNE) were increased, but endothelial nitricoxide synthase (eNOS), P-eNOS and vasodilator-stimulated phosphoprotein phosphorylation(P-VASP) were decreased. Catalase and superoxide dismutase (SOD-1 and SOD-2) proteins wereincreased, but glutathione peroxidase (GPx) was decreased in the aorta. Eu-A and atorvastatinreduced vasoconstrictor-induced aortic contractions that might be related to 5-HT1B/2A and a1-adrenergic receptors inhibitory activities. Eu-A and atorvastatin improved eNOS/P-eNOS, PVASP,GPx, and malondialdehyde (MDA) levels, and decreased ROS and oxidative damagemarkers. Taken together, we suggest that Eu-A can ameliorate hyperlipidemia-inducedvascular endothelial dysfunction and oxidative dysregulation.
關聯:
Kaohsiung Journal of Medical Sciences (2014) 30, 116e124
