title: Adrenergic activation confers cardioprotection mediated by adenosine, but is not required for ischemic preconditioning.
abstract: BACKGROUND
  The aim of this study was to determine whether (1) adrenergic activation is cardioprotective, (2) adrenergic cardioprotection occurs via adenosine receptor activation, and (3) ischemic preconditioning requires alpha-adrenergic activation.
  
  
  METHODS
  Anesthetised open chest rabbits underwent 30 min coronary occlusion and 3 h reperfusion. Ischemic preconditioning was elicited with 5 min coronary occlusion and 10 min reperfusion. Activation of adrenergic receptors with endogenous norepinephrine was achieved with tyramine (0.28 mg/kg/min intravenously for 5 min). Adenosine receptors were blocked with 8-p-sulfophenyl theophylline (10 mg/kg intravenously), alpha 1-adrenergic receptors were selectively blocked with prazosin (0.1 mg/kg intravenously), and alpha-adrenergic receptors were blocked with phentolamine (4 mg/kg intravenously).
  
  
  RESULTS
  Ischemic preconditioning reduced risk-adjusted infarct volume by 79% (P < 0.0005). This protection was attenuated by adenosine receptor blockade. Tyramine infusion resulted in a 1305% change from baseline plasma norepinephrine concentration (P < or = 0.01), and reduced infarct volume by 55% (P = 0.01). Adenosine receptor blockade abolished this protection. Blockade of alpha 1-adrenergic receptors with prazosin failed to abolish ischemic preconditioning (79 versus 89% reduction in infarct volume, without and with prazosin, respectively). Similarly, non-selective blockade of alpha-adrenergic receptors also failed to abolish ischemic preconditioning (79 versus 57% reduction without and with phentolamine, respectively).
  
  
  CONCLUSIONS
  We conclude that the cardioprotection of ischemic preconditioning and alpha-adrenergic activation both involve adenosine, but ischemic preconditioning does not require alpha-adrenergic activation.
authors.affiliation: Department of Anesthesiology, Oregon Health Sciences University, Portland, USA.
authors.forename: R
authors.initials: R
authors.lastname: Haessler
authors.forename: K
authors.initials: K
authors.lastname: Kuzume
authors.forename: R A
authors.initials: RA
authors.lastname: Wolff
authors.forename: K
authors.initials: K
authors.lastname: Kuzume
authors.forename: G L
authors.initials: GL
authors.lastname: Chien
authors.forename: R F
authors.initials: RF
authors.lastname: Davis
authors.forename: D M
authors.initials: DM
authors.lastname: Van Winkle
mesh_terms: D000241:Adenosine / Q000502:physiology*; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000818:Animals; D019157:Ischemic Preconditioning, Myocardial; D009203:Myocardial Infarction / Q000503:physiopathology; D009638:Norepinephrine / Q000502:physiology; D010646:Phentolamine / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D011817:Rabbits; D011941:Receptors, Adrenergic / Q000187:drug effects / Q000502:physiology*; D011942:Receptors, Adrenergic, alpha / Q000502:physiology; D013806:Theophylline / Q000494:pharmacology; D014439:Tyramine / Q000494:pharmacology
chemical_list: D000316:Adrenergic alpha-Agonists; D011941:Receptors, Adrenergic; D011942:Receptors, Adrenergic, alpha; D013806:Theophylline; D000241:Adenosine; D009638:Norepinephrine; D014439:Tyramine; D011224:Prazosin; D010646:Phentolamine