Open AccessEugenosedin‐A ameliorates hyperlipidemia‐induced vascular endothelial dysfunction via inhibition of α 1 ‐adrenoceptor/5‐HT activity and NADPH oxidase expression
Author(s) -
Shen KuoPing,
Lin HuiLi,
Chang WenTsan,
Lin JouChun,
An LiMei,
Chen IngJun,
Wu BinNan
Publication year - 2014
Publication title -
the kaohsiung journal of medical sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.439
H-Index - 36
eISSN - 2410-8650
pISSN - 1607-551X
DOI - 10.1016/j.kjms.2013.10.005
Subject(s) - enos , endothelial dysfunction , medicine , endocrinology , oxidative stress , nadph oxidase , superoxide dismutase , glutathione peroxidase , malondialdehyde , reactive oxygen species , hyperlipidemia , apocynin , asymmetric dimethylarginine , nitric oxide synthase , nitric oxide , chemistry , biochemistry , arginine , diabetes mellitus , amino acid
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 α 1 ‐adrenergic receptors (not 5‐HT 1B/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‐HT 1B/2A and α 1 ‐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.