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.
Bernardo
N L
NL
Division of Cardiology, Department of Medicine, Medical College of Virginia, Virginia Commonwealth University, Richmond, Virginia 23298, USA.
Okubo
S
S
Maaieh
M M
MM
Wood
M A
MA
Kukreja
R C
RC
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