title: Ryanodine receptor 2 contributes to hemorrhagic shock-induced bi-phasic vascular reactivity in rats.
abstract: OBJECTIVE
  Ryanodine receptor 2 (RyR2) is a critical component of intracellular Ca(2+) signaling in vascular smooth muscle cells (VSMCs). The aim of this study was to investigate the role of RyR2 in abnormal vascular reactivity after hemorrhagic shock in rats.
  
  
  METHODS
  SD rats were hemorrhaged and maintained mean arterial pressure (MAP) at 40 mmHg for 30 min or 2 h, and then superior mesenteric arteries (SMA) rings were prepared to measure the vascular reactivity. In other experiments, SMA rings of normal rats and rat VSMCs were exposed to a hypoxic medium for 10 min or 3 h. SMA rings of normal rats and VSMCs were transfected with siRNA against RyR2. Intracellular Ca(2+) release in VSMCs was assessed using Fura-2/AM.
  
  
  RESULTS
  The vascular reactivity of the SMA rings from hemorrhagic rats was significantly increased in the early stage (30 min), but decreased in the late stage (2 h) of hemorrhagic shock. Similar results were observed in the SMA rings exposed to hypoxia for 10 min or 3 h. The enhanced vascular reactivity of the SMA rings exposed to hypoxia for 10 min was partly attenuated by transfection with RyR2 siRNA, whereas the blunted vascular reactivity of the SMA rings exposed to hypoxia for 3 h was partly restored by transfection with RyR2 siRNA. Treatment with the RyR agonist caffeine (1 mmol/L) significantly increased Ca(2+) release in VSMCs exposed to hypoxia for 10 min or 3 h, which was partially antagonized by transfection with RyR2 siRNA.
  
  
  CONCLUSIONS
  RyR2-mediated Ca(2+) release contributes to the development of bi-phasic vascular reactivity induced by hemorrhagic shock or hypoxia.
authors.affiliation: State Key Laboratory of Trauma, Burns and Combined Injury, the 2nd Department of Research Institute of Surgery, Daping Hospital, the Third Military Medical University, Chongqing 400042, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Zhou
authors.affiliation: State Key Laboratory of Trauma, Burns and Combined Injury, the 2nd Department of Research Institute of Surgery, Daping Hospital, the Third Military Medical University, Chongqing 400042, China.
authors.forename: Xiao-li
authors.initials: XL
authors.lastname: Ding
authors.affiliation: State Key Laboratory of Trauma, Burns and Combined Injury, the 2nd Department of Research Institute of Surgery, Daping Hospital, the Third Military Medical University, Chongqing 400042, China.
authors.forename: Liang-ming
authors.initials: LM
authors.lastname: Liu
mesh_terms: D000818:Animals; D062186:Arterial Pressure; D002110:Caffeine / Q000494:pharmacology; D002120:Calcium Channel Agonists / Q000494:pharmacology; D020013:Calcium Signaling; D015687:Cell Hypoxia; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D017538:Mesenteric Artery, Superior / Q000378:metabolism / Q000503:physiopathology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism*; D009638:Norepinephrine / Q000494:pharmacology; D034622:RNA Interference; D017207:Rats, Sprague-Dawley; D019837:Ryanodine Receptor Calcium Release Channel / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D012519:Sarcoplasmic Reticulum / Q000378:metabolism; D012771:Shock, Hemorrhagic / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D013997:Time Factors; D014162:Transfection; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology
chemical_list: D002120:Calcium Channel Agonists; D019837:Ryanodine Receptor Calcium Release Channel; D014662:Vasoconstrictor Agents; D002110:Caffeine; D009638:Norepinephrine