Role of activation of ectosolic 5'-nucleotidase in the infarct
size-limiting effect mediated by the opening of k+ channels in canine
hearts: implication for the mechanisms of ischemic
preconditioning.
Kitakaze, Masafumi, Tetsuo Minamino, Koichi Node, Kazuo Komamura,
Yoshiro Shinozaki, Mitsuaki Chujo, Hidezo Mori, Michitoshi Inoue,
Masatsugu Hori, Takenobu Kamada.
The First Department of Medicine, Osaka University School of
Medicine, Osaka, Tokai University School of Medicine, Department of
Physiology II, Isehara, Department of Information Science, Osaka
University Hospital, Osaka, Japan
APStracts 2:0473A, 1995.
We tested the hypothesis that the opening of ATP-sensitive K+ channels
contributes to activation of ectosolic 5'-nucleotidase and the
infarct size-limiting effect of ischemic preconditioning. In the
open-chest dogs, the left anterior descending coronary artery was
occluded 4 times for 5 minutes each, separated by a 5-minute period
of reperfusion (ischemic preconditioning, n=8). After this procedure,
the coronary artery was occluded for 90 minutes, followed by 6 hours
of reperfusion. Infarct size was smaller in this group than in the
group (the control group, n=8) with a 45 minute-interval instead of
the ischemic preconditioning procedure (40.1+3.9 vs. 6.4+1.9%).
Glibenclamide blunted the infarct size-limiting effect of ischemic
preconditioning (infarct size: 37.3+5.8%, n=7), and transient
exposures to cromakalim and nicorandil mimicked it (infarct
size:10.1+3.1 (n=7) and 11.1+2.7% (n=8), respectively). Ectosolic and
cytosolic 5'-nucleotidase activity increased in the ischemic
preconditioning group compared with that in the control group; this
preconditioning-induced increase in 5'-nucleotidase activity was
blunted by glibenclamide (n=5) and mimicked by cromakalim (n=5) and
nicorandil (n=5). The infarct size-limiting effect due to cromakalim
and nicorandil was blunted by a,b,-methyleneadenosine 5'-diphosphate,
an inhibitor of ectosolic 5'-nucleotidase (infarct size:37.7+5.6
(n=9) and 36.8+4.8% (n=7), respectively), and 8
-sulfophenyltheophylline (infarct size with cromakalim: 44.7+4.6%
(n=7)). We conclude that activation of ectosolic 5'-nucleotidase due
to the openers of ATP-sensitive K+ channels contribute to the infarct
size-limiting effect of ischemic preconditioning.
Received 22 May 1995; accepted in final form 5 October 1995.
APS Manuscript Number A436-5.
Article publication pending Journal of Applied Physiology.
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 6 November 95