title: Betulinic acid inhibits superoxide anion-mediated impairment of endothelium-dependent relaxation in rat aortas.
abstract: OBJECTIVE
  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.
  
  
  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 EC(50) (2.0 μM) concentration of BA markedly enhanced ACh-induced EDR of aortas exposed to pyrogallol-produced superoxide anion (E(max) rose from 23.91 ± 5.41% to 42.45 ± 9.99%), which was markedly reversed by both N(w) -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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Clinical Research Center, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
authors.forename: Ling-Bo
authors.initials: LB
authors.lastname: Qian
authors.forename: Jia-Yin
authors.initials: JY
authors.lastname: Fu
authors.forename: Xin
authors.initials: X
authors.lastname: Cai
authors.forename: Man-Li
authors.initials: ML
authors.lastname: Xia
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000502:physiology; D008297:Male; D009924:Organ Culture Techniques; D053978:Pentacyclic Triterpenes; D051381:Rats; D017207:Rats, Sprague-Dawley; D013481:Superoxides / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D014315:Triterpenes / Q000494:pharmacology*; D014664:Vasodilation / Q000187:drug effects* / Q000502:physiology; D000094062:Betulinic Acid
chemical_list: D053978:Pentacyclic Triterpenes; D014315:Triterpenes; D013481:Superoxides; D000094062:Betulinic Acid
keywords: Betulinic acid; endothelium-dependent relaxation; nitric oxide oxidative stress; rat thoracic aorta