Eugenosedin-A ameliorates hyperlipidemia-induced vascular endothelial dysfunction via inhibition of α1-adrenoceptor/5-HT activity and NADPH oxidase expression.

Abstract

Eugenosedin-A (Eu-A) effects on vascular endothelial dysfunction and oxidative stress in a hyperlipidemic rat model were investigated. Rats were randomly divided into four groups: two control groups and two treatment groups. The control rats received a regular diet or high fat diet (HFD); the treatment rats fed received an HFD with 5 mg/kg Eu-A or atorvastatin for 10 weeks. No changes in serotonin levels were observed in the four groups; norepinephrine levels were enhanced in the HFD group which was attenuated by Eu-A and atorvastatin. In the HFD group, the vascular reactivity was increased by vasoconstrictors (5-nonyloxytryptamine, 5-HT, and phenylephrine) and decreased by an endothelium-dependent vasorelaxant, carbachol. Protein levels of α1-adrenergic receptors (not 5-HT1B/2A), reactive oxygen species (ROS) p47(phox), p67(phox), and gp91(phox), and oxidative damage markers 3-nitrotyrosine (3-NT) and 4-hydroxy-2-nonenal (4-HNE) were increased, but endothelial nitric oxide synthase (eNOS), P-eNOS and vasodilator-stimulated phosphoprotein phosphorylation (P-VASP) were decreased. Catalase and superoxide dismutase (SOD-1 and SOD-2) proteins were increased, but glutathione peroxidase (GPx) was decreased in the aorta. Eu-A and atorvastatin reduced vasoconstrictor-induced aortic contractions that might be related to 5-HT1B/2A and α1-adrenergic receptors inhibitory activities. Eu-A and atorvastatin improved eNOS/P-eNOS, P-VASP, GPx, and malondialdehyde (MDA) levels, and decreased ROS and oxidative damage markers. Taken together, we suggest that Eu-A can ameliorate hyperlipidemia-induced vascular endothelial dysfunction and oxidative dysregulation.

• Authors: Kuo-Ping Shen, Hui-Li Lin, Wen-Tsan Chang, Jou-Chun Lin, Li-Mei An, Ing-Jun Chen, Bin-Nan Wu
• Journal: The Kaohsiung journal of medical sciences (Kaohsiung J Med Sci) Vol. 30 Issue 3 Pg. 116-24 (Mar 2014) ISSN: 2410-8650 [Electronic] China (Republic : 1949- )
• PMID: 24581211 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013. Published by Elsevier B.V.

Chemical References

• Cell Adhesion Molecules
• Microfilament Proteins
• Phosphoproteins
• Piperazines
• Reactive Oxygen Species
• Receptors, Adrenergic
• eugenosedin-A
• vasodilator-stimulated phosphoprotein
• Serotonin
• Malondialdehyde
• Superoxide Dismutase
• NADPH Oxidases
• Norepinephrine

Topics

• Animals
• Aorta, Thoracic
• Brain (drug effects, metabolism)
• Cell Adhesion Molecules (metabolism)
• Endothelium, Vascular (drug effects, metabolism)
• Hyperlipidemias (complications)
• Male
• Malondialdehyde (metabolism)
• Microfilament Proteins (metabolism)
• NADPH Oxidases (metabolism)
• Norepinephrine (blood)
• Oxidative Stress (drug effects)
• Phosphoproteins (metabolism)
• Phosphorylation (drug effects)
• Piperazines (pharmacology)
• Rats
• Rats, Sprague-Dawley
• Reactive Oxygen Species (metabolism)
• Receptors, Adrenergic (metabolism)
• Serotonin (blood, metabolism)
• Superoxide Dismutase (metabolism)