title: Bradykinin induces vascular contraction after hemorrhagic shock in rats.
abstract: BACKGROUND
  Bradykinin (BK) has many biological effects in inflammation, allergy, and septic shock. Studies have shown that low doses of BK can induce vascular relaxation and high doses can induce vascular contraction in many pathophysiological conditions, but the role and mechanisms that high doses of BK have on vascular contraction in hemorrhagic shock are not clear.
  
  
  METHODS
  With hemorrhagic-shock rats and hypoxia-treated superior mesenteric artery (SMA), we investigated the role and mechanisms of high doses of BK-induced vascular contraction in hemorrhagic shock.
  
  
  RESULTS
  High doses of BK (500-50,000 ng/kg in vivo or 10(-10) to 10(-5) mol/L in vitro) dose dependently induced vascular contraction of SMA and increased the vascular calcium sensitivity in normal and hemorrhagic-shock rats. Less than 10(-10) mol/L of BK induced vascular dilation BK-induced increase of vascular contractile response and calcium sensitivity was reduced by denudation of the endothelium, 18α-glycyrrhetic acid (an inhibitor of myoendothelial gap junction) and connexin 43 antisense oligodeoxynucleotide. Further studies found that high concentrations of BK-induced vascular contraction in hemorrhagic shock was closely related to the activation of Rho A-Rho kinase pathway and Protein Kinase C (PKC) α and ε.
  
  
  CONCLUSIONS
  High doses of BK can induce vascular contraction in hemorrhagic shock condition, which is endothelium and myoendothelial gap junction dependent. Cx43-mediated activation of Rho A-Rho kinase and Protein Kinase C (PKC) pathway plays a very important role in this process. This finding provided a new angle of view to the biological role of BK in other pathophysiological conditions such as hemorrhagic shock or hypoxia.
authors.affiliation: State Key Laboratory of Trauma, Burns and Combined Injury, Second Department of Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing, P.R China.
authors.forename: Jie
authors.initials: J
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Trauma, Burns and Combined Injury, Second Department of Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing, P.R China.
authors.forename: Guang-ming
authors.initials: GM
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Trauma, Burns and Combined Injury, Second Department of Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing, P.R China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: State Key Laboratory of Trauma, Burns and Combined Injury, Second Department of Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing, P.R China.
authors.forename: Xiao-yong
authors.initials: XY
authors.lastname: Peng
authors.affiliation: State Key Laboratory of Trauma, Burns and Combined Injury, Second Department of Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing, P.R China. Electronic address: liangmingliu@yahoo.com.
authors.forename: Liang-ming
authors.initials: LM
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Trauma, Burns and Combined Injury, Second Department of Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing, P.R China. Electronic address: lt200132@163.com.
authors.forename: Tao
authors.initials: T
authors.lastname: Li
mesh_terms: D000818:Animals; D001920:Bradykinin / Q000494:pharmacology*; D018031:Connexin 43 / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D000860:Hypoxia / Q000188:drug therapy; D017538:Mesenteric Artery, Superior / Q000187:drug effects; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D051571:Protein Kinase C-alpha / Q000378:metabolism; D051744:Protein Kinase C-epsilon / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D012771:Shock, Hemorrhagic / Q000188:drug therapy* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects*; D014662:Vasoconstrictor Agents / Q000494:pharmacology*; D020830:rac1 GTP-Binding Protein / Q000378:metabolism; D054460:rho-Associated Kinases / Q000378:metabolism
chemical_list: D018031:Connexin 43; C580592:Gja1 protein, rat; D016376:Oligonucleotides, Antisense; D014662:Vasoconstrictor Agents; D054460:rho-Associated Kinases; D051571:Protein Kinase C-alpha; D051744:Protein Kinase C-epsilon; C499134:Rac1 protein, rat; D020830:rac1 GTP-Binding Protein; D001920:Bradykinin
keywords: Bradykinin; Connexin; PKC; Shock; Vascular reactivity