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 whether alpha 1-adrenoceptor stimulation in ischemic preconditioning mediates the infarct size-limiting effect through augmentation of 5'-nucleotidase activity. The coronary artery was occluded four times for 5 min separated by 5 min of reperfusion (ischemic preconditioning) in 82 dogs. Then the coronary artery was occluded for 90 min followed by 6 h of 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 endomyocardial collateral flow during ischemia (8.7 +/- 1.0 vs 8.9 +/- 1.0 ml/100 g per min). Ectosolic and cytosolic 5'-nucleotidase activity was increased 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 methoxamine mimicked the increase in 5'-nucleotidase activity and the infarct size-limiting effect, which were abolished by alpha, beta,-methyleneadenosine 5'-diphosphate. Identical results were obtained in the conscious model (n = 20). Therefore, we conclude that increases in ectosolic 5'-nucleotidase activity due to alpha 1-adrenoceptor activation may contribute to the infarct size-limiting effect of ischemic preconditioning.
Kitakaze
M
M
First Department of Medicine, Osaka University School of Medicine, Japan.
Hori
M
M
Morioka
T
T
Minamino
T
T
Takashima
S
S
Sato
H
H
Shinozaki
Y
Y
Chujo
M
M
Mori
H
H
Inoue
M
M
D015720:5'-Nucleotidase / Q000378:metabolism*; D000220:Adaptation, Biological; D000241:Adenosine / Q000097:blood; D000818:Animals; D001794:Blood Pressure; D004285:Dogs; D004699:Endocardium / Q000378:metabolism; D004947:Esophagus / Q000378:metabolism; D006439:Hemodynamics; D008729:Methoxamine / Q000494:pharmacology; D009203:Myocardial Infarction / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D017202:Myocardial Ischemia / Q000201:enzymology / Q000378:metabolism*; D010477:Perfusion; D011224:Prazosin / Q000494:pharmacology; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism*; D012307:Risk Factors
D018340:Receptors, Adrenergic, alpha-1; D015720:5'-Nucleotidase; D008729:Methoxamine; D000241:Adenosine; D011224:Prazosin