Betulinic acid inhibits superoxide anion-mediated impairment of endothelium-dependent relaxation in rat aortas |
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| Authors: | Ling-Bo Qian Jia-Yin Fu Xin Cai Man-Li Xia |
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| Institution: | 1Clinical Research Center, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China;2Institute of Physiological Function, Medical College of Jiaxing University, Jiaxing, China |
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| Abstract: | Objectives:To investigate the protective effect of betulinic acid (BA) on endothelium-dependent relaxation (EDR) in rat aortas exposed to pyrogallol-produced superoxide anion and its underlying mechanism.Materials and Methods:The thoracic aorta of male Sprague-Dawley rats was isolated to mount in the organ bath system and the effect of BA on acetylcholine (ACh)-induced EDR, nitric oxide (NO) level, reactive oxygen species (ROS) level, nitric oxide synthase (NOS) activity, and superoxide dismutase (SOD) activity of aortic rings exposed to pyrogallol (500 μM) for 15 min were measured.Results:BA evoked a concentration-dependent EDR in aortas, and pretreatment with EC50 (2.0 μM) concentration of BA markedly enhanced ACh-induced EDR of aortas exposed to pyrogallol-produced superoxide anion (Emax rose from 23.91 ± 5.41% to 42.45 ± 9.99%), which was markedly reversed by both Nw -nitro-L-arginine methyl ester hydrochloride (L-NAME) and methylene blue, but not by indomethacin. Moreover, BA significantly inhibited the increase of ROS level, as well as the decrease of NO level, the endothelial NOS (eNOS) activity, and the SOD activity in aortas induced by pyrogallol-derived superoxide anion.Conclusion:These results indicate that BA reduces the impairment of EDR in rat aortas exposed to exogenous superoxide anion, which may closely relate to the reduction of oxidative stress and activation of eNOS–NO pathway.KEY WORDS: Betulinic acid, endothelium-dependent relaxation, nitric oxide oxidative stress, rat thoracic aorta |
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