ISCHEMIA-REPERFUSION SELECTIVELY ATTENUATES CORONARY VASODILATATION TO AN ADENOSINE A(2)-AGONIST BUT NOT TO AN A(1)-AGONIST IN THE DOG

1 The effects of myocardial ischaemia/reperfusion were tested on the coronary vasorelaxant responses to agonists selective for the A1 and A2 adenosine receptor subtypes in the dog. The left anterior descending (LAD) coronary artery was occluded distal to the first diagonal branch. The occlusion was maintained for 1 h, followed by 1 h of reperfusion. 2 In the first series of experiments, LAD and circumflex arteries were excised and contracted with prostaglandin F2alpha (PGF2alpha). Ischaemia/reperfusion did not significantly alter the vasorelaxation produced by either sodium nitroprusside (endothelium-independent) or acetylcholine (endothelium-dependent). The A1 selective agonist, cyclopentyladenosine (CPA), produced coronary vasorelaxation in both normally perfused vessels and vessels subjected to ischaemia/reperfusion. In contrast, the relaxation produced by the A2-selective agonist N6-{2-(3,5-dimethoxyphenyl)-2-(2-methylphenyl) ethyl} adenosine (DPMA) was significantly attenuated by ischaemia/reperfusion (14 fold shift in EC50). 3 In the second series of experiments, coronary blood flow was increased by administration of the A1 and A2 agonists before and after ischaemia/reperfusion of the LAD in anaesthetized dogs. Both compounds dose-dependently increased coronary blood flow. The slopes of the dose-response functions to CPA or DPMA were not significantly altered in the normally perfused circumflex vascular bed. Similarly, the CPA dose-response function in the LAD was unaltered by ischaemia/reperfusion. However, the slope of the coronary vasodilator response to the A2 agonist was significantly reduced following ischaemia/reperfusion of the LAD. 4 We conclude that ischaemia/reperfusion reduces responsiveness to an adenosine A2 receptor subtype agonist, but not an A1 receptor subtype agonist. These data confirm the independent nature of A1- and A2-mediated coronary vasodilatation.