CARDIOPROTECTION PROVIDED BY ADENOSINE RECEPTOR ACTIVATION IS ABOLISHED BY BLOCKADE OF THE K-ATP CHANNEL

Cardioprotection provided by adenosine receptor activation is abolishe d by blockade of the K-ATP channel. Am. J. Physiol. 266 (Heart Circ. P hysiol. 35): H829-H839, 1994. - Adenosine agonists and openers of the ATP-sensitive potassium (K-ATP) channel have been reported to limit in farct size (IS). We tested the hypothesis that these phenomena are int erdependent. Anesthetized swine underwent 60 min of coronary artery oc clusion and 90 min of reperfusion. Preconditioning was elicited by two cycles comprising 10 min of occlusion and 10 min of reperfusion (n = 7 swine). An intracoronary infusion of adenosine (Ado; n = 10) or (-)- N-6-(2-phenylisopropyl)-adenosine (R-PLA; n = 7) replaced precondition ing ischemia. K-ATP channels were blocked with sodium 5-hydroxydecanoa te (5-HD) in the absence (n = 6) or presence (n = 8) ofR-PIA. Control pigs (n = 7) received saline vehicle. IS was assessed with tetrazolium and normalized as percentage of area at risk. Preconditioning resulte d in a reduced IS compared with Control (3.9 +/- 1.8 vs. 43.5 +/- 6.9% , respectively; P < 0.0005). Ado and R-PIA also reduced IS [21.1 +/- 6 .8 (P < 0.01) and 11.2 +/- 7.4% (P < 0.005), respectively]. 5-HD alone did not alter IS, but it abolished R-PIA-induced cardioprotection (IS 5-HD + R-PIA = 48.6 +/- 13.2%). Thus Ado A(1)-receptor agonists mimic ked the cardioprotection of ischemic preconditioning. The Ado-induced limitation of IS was abolished by blockade of the K-ATP channel. We co nclude that both Ado A(1) receptors and K-ATP channels may be involved in ischemic preconditioning.