Premium
Ischaemia/reperfusion selectively attenuates coronary vasodilatation to an adenosine A 2 ‐ but not to an A 1 ‐agonist in the dog
Author(s) -
Cox Bryan F.,
Greenland Brett D.,
Perrone Mark H.,
Merkel Linda A.
Publication year - 1994
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1994.tb14877.x
Subject(s) - adenosine , agonist , medicine , vasodilation , ischemia , sodium nitroprusside , coronary circulation , coronary vasodilator , cardiology , coronary occlusion , anesthesia , blood flow , nitric oxide , receptor
1 The effects of myocardial ischaemia/reperfusion were tested on the coronary vasorelaxant responses to agonists selective for the A 1 and A 2 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 F 2α (PGF 2α ). Ischaemia/reperfusion did not significantly alter the vasorelaxation produced by either sodium nitroprusside (endothelium‐independent) or acetylcholine (endothelium‐dependent). The A 1 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 A 2 ‐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 A 1 and A 2 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 A 2 agonist was significantly reduced following ischaemia/reperfusion of the LAD. 4 We conclude that ischaemia/reperfusion reduces responsiveness to an adenosine A 2 receptor subtype agonist, but not an A 1 receptor subtype agonist. These data confirm the independent nature of A 1 and A 2 ‐mediated coronary vasodilatation.