Mjp. Raatikainen et al., CONTRIBUTION OF ENDOTHELIUM AND CARDIOMYOCYTES TO HYPOXIA-INDUCED ADENOSINE RELEASE, Journal of Molecular and Cellular Cardiology, 26(8), 1994, pp. 1069-1080
The cellular source and role of adenosine in hypoxia-induced coronary
vasodilatation was investigated. The endothelial adenine nucleotides o
f Langendorff-perfused rat hearts were prelabelled by perfusion with [
H-3]adenosine and the changes in specific radioactivities were employe
d to identify the source of the adenine compounds released. The contri
bution of ecto-5'-nucleotidase was evaluated in perfusions with the in
hibitor alpha,beta-methylene adenosine diphosphate (AOPCP). Absorbance
of the effluent perfusate at 260nm was monitored continuously as a co
nvenient means of detecting the output of total purines, and it showed
a good correlation with HPLC-measured purines (r=0.72, P < 0.001). Co
ronary Bow increased sharply in hypoxia but tended to decrease after 2
min, while effluent radiaoctivity and absorbance increased steadily.
The radioactivity-to-absorbance ratio and the specific radioactivity o
f chemically measured total purines began to increase after 3 min. The
changes in effluent concentrations of adenosine and inosine were much
more prominent than those in free purines. The specific radioactivity
of adenosine decreased sharply at the onset of hypoxia which indicate
s that hypoxia affects mainly working cardiomyocytes. This also means
that endothelial adenosine release is delayed if compared to coronary
vasoregulation. Although the inhibition of ecto-5'-nucleotidase caused
a decrease in the release of adenosine and adenine moiety label from
the heart it is most likely that adenosine was mainly derived from int
racellular sources, because the hypoxia-induced increase in the concen
tration of adenosine was more excessive than that of AMP. In addition,
AOPCP decreased the basal work load and coronary now of the heart, sl
ightly attenuated the hypoxia-induced Bow increase and prevented adeny
late loss during hypoxia. Thus, the data emphasize the role of cardiom
yocytes in adenosine production and coronary vasoregulation.