title: Beta-adrenoceptor blocker carvedilol provides cardioprotection via an adenosine-dependent mechanism in ischemic canine hearts.
abstract: BACKGROUND
  Carvedilol is a beta-adrenoceptor blocker with a vasodilatory action that is more effective for the treatment of congestive heart failure than other beta-blockers. Recently, carvedilol has been reported to reduce oxidative stress, which may consequently reduce the deactivation of adenosine-producing enzymes and increase cardiac adenosine levels. Therefore, carvedilol may also have a protective effect on ischemia and reperfusion injury, because adenosine mediates cardioprotection in ischemic hearts.
  
  
  RESULTS
  In anesthetized dogs, the left anterior descending coronary artery was occluded for 90 minutes, followed by reperfusion for 6 hours. Carvedilol reduced the infarct size (15.0+/-2.8% versus 40.9+/-4.2% in controls), and this effect was completely reversed by the nonselective adenosine receptor antagonist 8-sulfophenyltheophylline (45.2+/-5.4%) or by an inhibitor of ecto-5'-nucleotidase (44.4+/-3.6%). There were no differences of either area at risk or collateral flow among the various groups. When the coronary perfusion pressure was reduced in other dogs so that coronary blood flow was decreased to 50% of the nonischemic level, carvedilol increased coronary blood flow (49.4+/-5.6 to 73.5+/-7.5 mL x 100 g(-1) x min(-1); P<0.05) and adenosine release (112.3+/-22.2 to 240.6+/-57.1 nmol/L; P<0.05) during coronary hypoperfusion. This increase of coronary blood flow was attenuated by either 8-sulfophenyltheophylline or superoxide dismutase. In human umbilical vein endothelial cells cultured with or without xanthine and xanthine oxidase, carvedilol caused an increase of ecto-5'-nucleotidase activity.
  
  
  CONCLUSIONS
  Carvedilol shows a cardioprotective effect against ischemia and/or reperfusion injury via adenosine-dependent mechanisms.
authors.affiliation: Department of Internal Medicine and Therapeutics, Osaka University Graduate School of Medicine, Suita, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Asanuma
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Minamino
authors.forename: Shoji
authors.initials: S
authors.lastname: Sanada
authors.forename: Seiji
authors.initials: S
authors.lastname: Takashima
authors.forename: Hisakazu
authors.initials: H
authors.lastname: Ogita
authors.forename: Akiko
authors.initials: A
authors.lastname: Ogai
authors.forename: Masanori
authors.initials: M
authors.lastname: Asakura
authors.forename: Yulin
authors.initials: Y
authors.lastname: Liao
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Asano
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Shintani
authors.forename: Jiyoong
authors.initials: J
authors.lastname: Kim
authors.forename: Yoshiro
authors.initials: Y
authors.lastname: Shinozaki
authors.forename: Hidezo
authors.initials: H
authors.lastname: Mori
authors.forename: Koichi
authors.initials: K
authors.lastname: Node
authors.forename: Soichiro
authors.initials: S
authors.lastname: Kitamura
authors.forename: Hitonobu
authors.initials: H
authors.lastname: Tomoike
authors.forename: Masatsugu
authors.initials: M
authors.lastname: Hori
authors.forename: Masafumi
authors.initials: M
authors.lastname: Kitakaze
mesh_terms: D015720:5'-Nucleotidase / Q000378:metabolism; D000241:Adenosine / Q000378:metabolism / Q000502:physiology*; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D002227:Carbazoles / Q000494:pharmacology* / Q000627:therapeutic use; D000077261:Carvedilol; D002478:Cells, Cultured; D003326:Coronary Circulation / Q000187:drug effects*; D004285:Dogs; D006801:Humans; D009203:Myocardial Infarction / Q000188:drug therapy / Q000473:pathology; D017202:Myocardial Ischemia / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D011412:Propanolamines / Q000494:pharmacology* / Q000627:therapeutic use; D011433:Propranolol / Q000494:pharmacology
chemical_list: D000319:Adrenergic beta-Antagonists; D002227:Carbazoles; D011412:Propanolamines; D000077261:Carvedilol; D011433:Propranolol; D015720:5'-Nucleotidase; D000241:Adenosine