M. Kitakaze et al., ROLE OF ACTIVATION OF ECTOSOLIC 5'-NUCLEOTIDASE IN THE CARDIOPROTECTION MEDIATED BY OPENING OF K+ CHANNELS, American journal of physiology. Heart and circulatory physiology, 39(5), 1996, pp. 1744-1756
We tested the hypothesis that the opening of ATP-sensitive K+ channels
contributes to activation of ectosolic 5'-nucleotidase and the infarc
t size-limiting effect of ischemic preconditioning. In open-chest dogs
, the left anterior descending coronary artery was occluded four times
for 5 min each, separated by a 5-min period of reperfusion (ischemic
preconditioning, n = 8). After this procedure, the coronary artery was
occluded for 90 min, followed by 6 h of reperfusion. Infarct size was
smaller in this group than in the group (control, n = 8) with a 45-mi
n interval instead of the ischemic preconditioning procedure (40.1 +/-
3.9 vs. 6.4 +/- 1.9%). Glibenclamide blunted the infarct size-limitin
g 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), respect
ively]. Ectosolic and cytosolic 5'-nucleotidase activity increased in
the ischemic preconditioning group compared with that in the control g
roup; this pre conditioning-induced increase in 5'-nucleotidase activi
ty was blunted by glibenclamide (n = 5) and mimicked by cromakalim (n
= 5) and nicorandil (n = 5). The infarct size-limiting effect due to c
romakalim and nicorandil was blunted by alpha,beta-methyleneadenosine
5'-diphosphate, an inhibitor of ectosolic 5'-nucleotidase [infarct siz
e, 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 contributes to the infarct
size-limiting effect of ischemic preconditioning.