Delayed preconditioning with adenosine is mediated by opening of ATP-sensitive K + channels in rabbit heart

• Published in: American journal of physiology. Heart and circulatory physiology 1999-07, Vol.277 (1), p.H128
• Main Authors: Bernardo, Nelson L, Okubo, Shinji, Maaieh, Mohammed M, Wood, Mark A, Kukreja, Rakesh C
• Format: Article
• Language: English
• ISSN: 1522-1539

The adenosine agonist 2-chloro- N -cyclopentyladenosine (CCPA) induces delayed ischemic protection in vivo. We hypothesized that this protection is mediated by opening of ATP-sensitive K (K ) 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 -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 channels but does not involve the synthesis of HSP 72.