Release of
adenosine and
AMP into epicardial fluid and coronary venous effluent of isovolumic guinea-pig hearts was examined during normoxic (95% O2) and hypoxic (30% O2) perfusion with and without the
ecto-5'-nucleotidase inhibitor alpha,beta-methylene
adenosine diphosphate (
AOPCP)*. Normoxic epicardial and venous
adenosine levels were 221 +/- 27 and 67 +/- 11 nM, respectively, in untreated hearts. During 15 min of
hypoxia, epicardial and venous
adenosine levels increased in a phasic manner, reaching maximal values of 498 +/- 32 and 441 +/- 43 nM, respectively, during the initial 5 min of
hypoxia. Epicardial and venous
adenosine levels then declined slightly during the subsequent 10 min to 332 +/- 33 and 224 +/- 34 nM, respectively. Infusion of 50 microM
AOPCP significantly reduced venous
adenosine levels during normoxia (less than 50% of control), but was without effect on normoxic epicardial
adenosine. Epicardial and venous
adenosine levels increased during
hypoxia with
AOPCP but the increases were lower than those for untreated hypoxic hearts. Epicardial and venous
adenosine levels recovered to baseline levels following 30 min of reoxygenation in both groups. Epicardial and venous
AMP levels were elevated by
AOPCP treatment during normoxia and
hypoxia. Coronary vascular resistance decreased during
hypoxia but the decline in resistance was less in
AOPCP treated hearts. It is concluded that whereas basal interstitial
adenosine levels appear to be independent of
ecto-5'-nucleotidase activity, the hypoxic increase in interstitial
adenosine is partially derived from an
AOPCP sensitive
ecto-5'-nucleotidase. Venous
adenosine appears to be significantly dependent on
ecto-5'-nucleotidase activity during normoxia and
hypoxia.(ABSTRACT TRUNCATED AT 250 WORDS)