Delayed preconditioning with adenosine is mediated by opening of ATP-sensitive K(+) channels in rabbit heart.
The adenosine agonist 2-chloro-N(6)-cyclopentyladenosine (CCPA) induces delayed ischemic protection in vivo. We hypothesized that this protection is mediated by opening of ATP-sensitive K(+) (K(ATP)) channels and increased synthesis of 72-kDa heat shock protein (HSP 72). Six groups (n = 9-13 animals/group) of animals were studied: group I, control rabbits that received no treatment; group II, animals given glibenclamide (0.3 mg/kg iv) 30 min before ischemia; group III, animals given 5-hydroxydecanoate (5-HD; 5 mg/kg iv) 15 min before ischemia; group IV, rabbits treated with CCPA (0.1 mg/kg iv) 24 h before ischemia; and groups V and VI, CCPA-treated animals that received the K(ATP)-channel blockers glibenclamide or 5-HD, respectively, 30 or 15 min before ischemia. All animals were subjected to ischemia by 30 min of coronary artery occlusion followed by 3 h of reperfusion. Risk area was delineated by injection of 10% Evans blue dye, and infarct size was determined by triphenyltetrazolium staining. Action potential duration (APD) was measured with an epicardial electrode. HSP 72 was measured by Western blotting. CCPA caused a significant reduction in infarct size [12.02 +/- 1.0 vs. 40.0 +/- 3.8% (%area at risk) in controls, P < 0.01] that was blocked by glibenclamide (36.2 +/- 3.1%, P < 0.01) and 5-HD (35.0 +/- 2.9%, P < 0.01). Glibenclamide and 5-HD did not change infarct size in control rabbits. These blockers significantly suppressed ischemia-induced APD shortening in control and CCPA-treated animals. CCPA treatment did not induce HSP 72 in hearts. These data suggest that adenosine-initiated delayed protection is mediated via opening of K(ATP) channels but does not involve the synthesis of HSP 72.
Division of Cardiology, Department of Medicine, Medical College of Virginia, Virginia Commonwealth University, Richmond, Virginia 23298, USA.
N L
NL
Bernardo
S
S
Okubo
M M
MM
Maaieh
M A
MA
Wood
R C
RC
Kukreja
D000200:Action Potentials; D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology*; D000255:Adenosine Triphosphate / Q000502:physiology*; D000818:Animals; D002317:Cardiovascular Agents / Q000494:pharmacology*; D019157:Ischemic Preconditioning, Myocardial; D008297:Male; D009203:Myocardial Infarction / Q000473:pathology; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology*; D011817:Rabbits; D013997:Time Factors
D002317:Cardiovascular Agents; D015221:Potassium Channels; C058394:2-chloro-N(6)cyclopentyladenosine; D000255:Adenosine Triphosphate; D000241:Adenosine