title: Astragaloside IV improves the isoproterenol-induced vascular dysfunction via attenuating eNOS uncoupling-mediated oxidative stress and inhibiting ROS-NF-κB pathways.
abstract: OBJECTIVE
  Oxidative stress and inflammation are regarded as two important triggers of endothelial dysfunction and play pivotal role in progression of vascular damage associated with cardiac hypertrophy. Our previous studies demonstrated that astragaloside IV (AsIV) could protect against cardiac hypertrophy in rats induced by isoproterenol (Iso), but its effects on the aorta are not known. In present study, we aimed to assess the effects of AsIV on Isoinduced vascular dysfunction.
  
  
  METHODS
  Sprague-Dawley (SD) rats were treated with Iso (10mg/kg/d) alone or in combination with AsIV (50mg/kg/d).
  
  
  RESULTS
  Compared with Isotreated alone, AsIV significantly reduced the ratios of heart weight/body weight and left ventricular weight/body weight. AsIV ameliorated the increased vasoconstriction response to phenylephrine induced by Iso and suppressed superoxide anion generation in rat aorta, increased endothelial nitric oxide synthase (eNOS) dimer/monomer ratio and its critical cofactor tetrahydrobiopterin (BH4) content in aorta as well as the NO production in the serum, reduced the plasmatic peroxynitrite (ONOO-). Moreover, in contrast with Isotreatment alone, AsIV decreased the ratio of nuclear-to-cytosolic protein expression of the NF-κB p65 subunit while enhanced its inhibited protein expression of IκB-α, down-regulated mRNA expression of IL-1β, IL-6 and TNF-α of the aorta.
  
  
  CONCLUSIONS
  The present study suggested that AsIV protects against Isoinduced vascular dysfunction probably via attenuating eNOS uncoupling-mediated oxidative stress and inhibiting ROS-NF-κB pathways.
authors.affiliation: Key Laboratory of Cardiovascular and Cerebrovascular Drug Research of Liaoning Province, Liaoning Medical College, Jinzhou 121001, China.
authors.forename: Chonghua
authors.initials: C
authors.lastname: Xu
authors.affiliation: Key Laboratory of Cardiovascular and Cerebrovascular Drug Research of Liaoning Province, Liaoning Medical College, Jinzhou 121001, China.
authors.forename: Futian
authors.initials: F
authors.lastname: Tang
authors.affiliation: Key Laboratory of Cardiovascular and Cerebrovascular Drug Research of Liaoning Province, Liaoning Medical College, Jinzhou 121001, China.
authors.forename: Meili
authors.initials: M
authors.lastname: Lu
authors.affiliation: Key Laboratory of Cardiovascular and Cerebrovascular Drug Research of Liaoning Province, Liaoning Medical College, Jinzhou 121001, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Yang
authors.affiliation: Key Laboratory of Cardiovascular and Cerebrovascular Drug Research of Liaoning Province, Liaoning Medical College, Jinzhou 121001, China.
authors.forename: Ronghui
authors.initials: R
authors.lastname: Han
authors.affiliation: Key Laboratory of Cardiovascular and Cerebrovascular Drug Research of Liaoning Province, Liaoning Medical College, Jinzhou 121001, China.
authors.forename: Meng
authors.initials: M
authors.lastname: Mei
authors.affiliation: Key Laboratory of Cardiovascular and Cerebrovascular Drug Research of Liaoning Province, Liaoning Medical College, Jinzhou 121001, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Hu
authors.affiliation: Key Laboratory of Cardiovascular and Cerebrovascular Drug Research of Liaoning Province, Liaoning Medical College, Jinzhou 121001, China.
authors.forename: Mingsheng
authors.initials: M
authors.lastname: Zhou
authors.affiliation: Key Laboratory of Cardiovascular and Cerebrovascular Drug Research of Liaoning Province, Liaoning Medical College, Jinzhou 121001, China. Electronic address: hongxinwang@lnmu.edu.cn.
authors.forename: Hongxin
authors.initials: H
authors.lastname: Wang
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D001011:Aorta / Q000187:drug effects* / Q000502:physiology; D027885:Astragalus propinquus / Q000276:immunology*; D006332:Cardiomegaly / Q000139:chemically induced / Q000188:drug therapy*; D016207:Cytokines / Q000378:metabolism; D006801:Humans; D007545:Isoproterenol / Q000008:administration & dosage; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D058451:Oxidative Coupling / Q000187:drug effects; D016491:Peripheral Vascular Diseases / Q000139:chemically induced / Q000188:drug therapy*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D012503:Saponins / Q000627:therapeutic use*; D015398:Signal Transduction / Q000187:drug effects; D014315:Triterpenes / Q000627:therapeutic use*
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; D016328:NF-kappa B; D017382:Reactive Oxygen Species; D012503:Saponins; D014315:Triterpenes; C052064:astragaloside A; D052250:Nitric Oxide Synthase Type III; D007545:Isoproterenol
keywords: Astragaloside IV; Isoproterenol; NF-κB; Tetrahydrobiopterin; eNOS uncoupling