Release of adenosine, inosine and hypoxanthine from the isolated guinea pig heart during hypoxia, flow-autoregulation and reactive hyperemia.

In an attempt to test the hypothesis whether adenosine is involved in the regulation of coronary flow adenosine, inosine and hypoxanthine were measured in the effluent perfusate and in the tissue of isolated guinea pig hearts under various experimental conditions. In addition, the release of 14C-adenosine, 14C-inosine and 14C-hypoxanthine was determined after prelabeling cardiac adenine nucleotides with 14C-adenine. The decrease in coronary resistance induced by hypoxic perfusion (30% and 20% in the gas phase) and during autoregulation was associated with a considerable increase in the release of adenosine and hypoxanthine. Under both conditions the concentrations of adenosine in the effluent perfusate were clearly within the coronary vasodilating range of exogenously administered adenosine. The tissue content of adenosine also increased significantly when the perfusion pressure was reduced. The release of 14C-adenosine closely paralleled the changes in coronary resistance during hypoxic perfusion, autoregulation and during reactive hyperemia. The specific activity of adenosine in the effluent perfusate, however, decreased substantially upon reduction of the oxygen supply to the heart, indicating that the release of 14C-adenosine does not provide an absolute measure of total adenosine release by the heart. Our data indicate that the greater part of the adaptive changes of vascular resistance during hypoxia and autoregulation can be attributed to adenosine which is formed at an enhanced rate under these conditions. However, other factors might be involved as well.