title: Adenosine-A1 receptors activation restores the suppressed cardioprotective effects of ischemic preconditioning in hyperhomocysteinemic rat hearts.
abstract: BACKGROUND
  We have previously shown that the cardioprotective effect of ischemic preconditioning (IPC) is suppressed in hyperhomocysteinemic rat hearts. The present study investigated the effect of 2-chloro-N-cyclopentyladenosine (CCPA), a selective adenosine-A1 receptor agonist, in hyperhomocysteinemia-induced attenuation of the cardioprotective effect of IPC.
  
  
  METHODS
  Rats were administered L-methionine (1.7 g/kg/day po) for 8 weeks to produce hyperhomocysteinemia. Isolated Langendorff perfused normal and hyperhomocysteinemic rat hearts were subjected to 30-minute global ischemia, followed by a 120-minute reperfusion. Myocardial infarct size was assessed macroscopically using triphenyltetrazolium chloride staining. Coronary effluent was analyzed for lactate dehydrogenase and CK-MB release to assess the extent of cardiac injury. The oxidative stress in the heart was assessed by measuring thiobarbituric acid reactive substance and reduced form of glutathione.
  
  
  RESULTS
  Ischemia and reperfusion (I/R) produced myocardial injury by increasing myocardial infarct size, elevating lactate dehydrogenase and CK-MB release in coronary effluent, decreasing coronary flow rate, and inducing oxidative stress in normal and hyperhomocysteinemic rat hearts. The hyperhomocysteinemic rat hearts showed enhanced I/R-induced myocardial injury with high oxidative stress. The IPC afforded cardioprotection against I/R-induced myocardial injury in normal rat hearts. However, IPC-mediated myocardial protection against I/R injury was abolished in hyperhomocysteinemic rat hearts. Administration of CCPA did not alter the cardioprotective effect of IPC in normal rat hearts, but its administration markedly restored the cardioprotective effect of IPC in hyperhomocysteinemic rat hearts.
  
  
  CONCLUSIONS
  It may be concluded that the activation of adenosine-A1 receptors using CCPA markedly restored the suppressed cardioprotective and infarct size-limiting effects of IPC in hyperhomocysteinemic rat hearts. Thus, the reduced availability of extracellular adenosine and impaired activation of adenosine-A1 receptors may be responsible for abolishing the cardioprotective potential of IPC against I/R-induced myocardial injury in hyperhomocysteinemic rat hearts.
authors: Cardiovascular Pharmacology Division, ISF College of Pharmacy, Moga, Punjab, India. pbala2006@gmail.com
authors: Pitchai
authors: P
authors: Balakumar
authors: Harsimran
authors: H
authors: Singh
authors: Krishna
authors: K
authors: Reddy
authors: Madhu B
authors: MB
authors: Anand-Srivastava
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D058907:Adenosine A1 Receptor Agonists; D000818:Animals; D002316:Cardiotonic Agents / Q000494:pharmacology*; D052279:Creatine Kinase, MB Form / Q000378:metabolism; D005260:Female; D005978:Glutathione / Q000378:metabolism; D006321:Heart / Q000187:drug effects / Q000503:physiopathology; D006352:Heart Ventricles / Q000187:drug effects / Q000378:metabolism; D020138:Hyperhomocysteinemia / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology*; D066298:In Vitro Techniques; D019157:Ischemic Preconditioning, Myocardial; D045022:Lactate Dehydrogenases / Q000378:metabolism; D008297:Male; D008715:Methionine / Q000633:toxicity; D009203:Myocardial Infarction / Q000473:pathology; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy / Q000378:metabolism / Q000517:prevention & control; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D012720:Severity of Illness Index; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
chemical_list: D058907:Adenosine A1 Receptor Agonists; D002316:Cardiotonic Agents; D017392:Thiobarbituric Acid Reactive Substances; C058394:2-chloro-N(6)cyclopentyladenosine; D008715:Methionine; D045022:Lactate Dehydrogenases; D052279:Creatine Kinase, MB Form; D005978:Glutathione; D000241:Adenosine