ALPHA(1)-ADRENOCEPTOR ACTIVATION MEDIATES THE INFARCT SIZE-LIMITING EFFECT OF ISCHEMIC PRECONDITIONING THROUGH AUGMENTATION OF 5'-NUCLEOTIDASE ACTIVITY

We have reported that ischemic preconditioning may limit infarct size by increasing 5'-nucleotidase activity. The present study tested wheth er alpha(1)-adrenoceptor stimulation in ischemic preconditioning media tes the infarct size-limiting effect through augmentation of 5'-nucleo tidase activity. The coronary artery was occluded four times for 5 min separated by 5 min of reperfusion (ischemic preconditioning) in 82 do gs. Then the coronary artery was occluded for 90 min followed by 6 h o f reperfusion. Infarct size normalized by risk area was smaller after ischemic preconditioning than in the control group (40.6 +/- 2.3 vs 6. 7 +/- 2.0%, P < 0.001), even though no difference existed in endomyoca rdial collateral flow during ischemia (8.7 +/- 1.0 vs 8.9 +/- 1.0 ml/1 00 g per min). Ectosolic and cytosolic 5'-nucleotidase activity was in creased after ischemic preconditioning. However, prazosin blunted the infarct size-limiting effect of ischemic preconditioning (infarct size : 42.8 +/- 3.7%). Intermittent alpha(1)-adrenoceptor stimulation by me thoxamine mimicked the increase in 5'-nucleotidase activity and the in farct size-limiting effect, which were abolished by alpha, beta,-methy leneadenosine 5'-diphosphate. Identical results were obtained in the c onscious model (n = 20). Therefore, we conclude that increases in ecto solic 5'-nucleotidase activity due to alpha(1)-adrenoceptor activation may contribute to the infarct size-limiting effect of ischemic precon ditioning.