To determine whether adenosine A3 receptors participate in adenosine-induced changes in coronary flow, isolated hearts from wild-type (WT) and A3 receptor knockout (A3KO) mice were perfused under constant pressure and effects of nonselective and selective agonists were examined. Adenosine and the selective A2A agonist 2-[p-(2-carboxyethyl)]phenylethylamino-5′-N-ethylcarboxamidoadenosine (CGS-21680) produced augmented maximal coronary vasodilation in A3KO hearts compared with WT hearts. Selective activation of A3 receptors with 2-chloro-N6(3-iodobenzyl)-adenosine-5′-N-methyluronamide (Cl-IB-MECA) at nanomolar concentrations did not effect coronary flow, but at higher concentrations it produced coronary vasodilation both in WT and A3KO hearts. Cl-IB-MECA-induced increases in coronary flow were susceptible to both pharmacological blockade and genetic deletion of A2A receptors. Because deletion or blockade of adenosine A3 receptors augmented coronary flow induced by nonselective adenosine and the selective A2A receptor agonist CGS-21680, we speculate that this is due to removal of an inhibitory influence associated with the A3 receptor subtype. These data indicate that the presence of adenosine A3 receptors may either inhibit or negatively modulate coronary flow mediated by other adenosine receptor subtypes.
|Original language||English (US)|
|Journal||American Journal of Physiology - Heart and Circulatory Physiology|
|Issue number||6 51-6|
|State||Published - 2002|
All Science Journal Classification (ASJC) codes
- Cardiology and Cardiovascular Medicine
- Physiology (medical)