To clarify which adenosine receptor subtype(s) are responsible for regulation of coronary flow through endogenous adenosine, coronary vascular responses were examined in isolated hearts from wild-type (WT) and A2A knockout (A2AKO) mice. Adenosine deaminase inhibitor, erythro-9-hydroxy-nonyladenine (EHNA), and adenosine kinase inhibitor, iodotubericidine (ITU), were used to examine the effects of endogenous adenosine. Combined infusion of EHNA and ITU in Balb/c hearts produced comparable increases in coronary flow as exerted by exogenous adenosine while they markedly decreased the heart rate, and these effects were reversed by adenosine receptor antagonist, 8-p-sulfophenyl-theophylline (8-SPT). Similarly, EHNA and ITU increased coronary flow in WT hearts to 422% of baseline, whereas this response was reduced to 144% of baseline in A2AKO hearts. Heart rate was equally reduced (approximately 50% of baseline) in both groups. Alloxazine (A2B receptor antagonist) abolished EHNA- and ITU-induced coronary flow in A2AKO hearts without altering the reduced heart rate. Selective A1 receptor antagonist, 8-cyclopentyl-1-1,3-dipropylxanthine (DPCPX), reversed EHNA- and ITU-induced decreases in heart rate without altering the elevated coronary flow. These findings suggest that coronary vascular responses to endogenous adenosine mimic those produced by exogenous adenosine and are mediated at least by activation of both A2A and A2B receptors in isolated mouse hearts.
All Science Journal Classification (ASJC) codes
- Cardiology and Cardiovascular Medicine