title: Adenosine A(2A)R modulates cardiovascular function by activating ERK1/2 signal in the rostral ventrolateral medulla of acute myocardial ischemic rats.
abstract: OBJECTIVE
  To investigate the cardiovascular regulatory mechanism of adenosine A(2A) receptor (A(2A)R) in the rostral ventrolateral medulla (RVLM) in acute myocardial ischemic (AMI) rats.
  
  
  METHODS
  The animal model of AMI was established by ligating the left anterior descending coronary artery (LAD). The A(2A)R expression was examined by immunohistochemistry, western blot and real-time PCR. CGS21680 and SCH58261 (an agonist and antagonist of A(2A)R) were respectively microinjected into the RVLM. In a subgroup of rats, PD98059 (an antagonist of extracellular signal-regulated kinase (ERK1/2)) was microinjected prior to CGS21680 administration. Phosphorylation of ERK1/2 was examined by western blot.
  
  
  RESULTS
  Our results demonstrated that A(2A)R immunoreactive positive neurons, the expressions of protein and mRNA of A(2A)R in the RVLM of AMI group were increased compared with the sham group. Microinjection CGS21680 into the RVLM inhibited mean arterial pressure (MAP) and heart rate (HR) in both AMI and sham groups. The inhibition was significantly greater in AMI group than in sham group. The cardiovascular effects of CGS21680 mentioned above were almost abolished by prior administration of PD98059. The increase of ERK1/2 in the RVLM with the cardiovascular responses was induced by CGS21680 in AMI rats; this effect was also blocked by SCH58261.
  
  
  CONCLUSIONS
  This study reveals that the activated A(2A)R in the RVLM underlies the depressor and bradycardiac responses in AMI rats via phosphorylation of ERK1/2 increasing.
authors.affiliation: Department of Physiology and Pathophysiology, Shanghai Medical College of Fudan University, China.
authors.forename: Meiyan
authors.initials: M
authors.lastname: Jiang
authors.forename: Chengrong
authors.initials: C
authors.lastname: Zhang
authors.forename: Jin
authors.initials: J
authors.lastname: Wang
authors.forename: Jun
authors.initials: J
authors.lastname: Chen
authors.forename: Chunmei
authors.initials: C
authors.lastname: Xia
authors.forename: Dongshu
authors.initials: D
authors.lastname: Du
authors.forename: Na
authors.initials: N
authors.lastname: Zhao
authors.forename: Yinxiang
authors.initials: Y
authors.lastname: Cao
authors.forename: Linlin
authors.initials: L
authors.lastname: Shen
authors.forename: Danian
authors.initials: D
authors.lastname: Zhu
mesh_terms: D000208:Acute Disease; D058908:Adenosine A2 Receptor Agonists / Q000494:pharmacology; D058917:Adenosine A2 Receptor Antagonists / Q000494:pharmacology; D000818:Animals; D015153:Blotting, Western; D002320:Cardiovascular Physiological Phenomena; D004789:Enzyme Activation / Q000502:physiology; D006439:Hemodynamics / Q000502:physiology; D007150:Immunohistochemistry; D008297:Male; D008526:Medulla Oblongata / Q000502:physiology*; D008845:Microinjections; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D048052:Mitogen-Activated Protein Kinase 3 / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D017202:Myocardial Ischemia / Q000503:physiopathology*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D043705:Receptor, Adenosine A2A / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D058908:Adenosine A2 Receptor Agonists; D058917:Adenosine A2 Receptor Antagonists; D047428:Protein Kinase Inhibitors; D012333:RNA, Messenger; D043705:Receptor, Adenosine A2A; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3