Adenosine is known to regulate myocardial and coronary circulatory functions.
Adenosine not only dilates coronary vessels, but attenuates
beta-adrenergic receptor-mediated increases in myocardial contractility and depresses both sinoatrial and atrioventricular node activities. The effects of
adenosine are mediated by two distinct receptors (i.e., A1 and A2 receptors). A1
adenosine receptors, located in atrial and ventricular myocardium and sinoatrial/atrioventricular nodes, are responsible for inhibition of
adenylyl cyclase activity. A2
adenosine receptors, located in coronary endothelial and smooth muscle cells, are responsible for stimulation of this
enzyme activity. During increased myocardial
oxygen demand due to rapid pacing and exercise, although both coronary blood flow and
adenosine concentrations in the myocardium and coronary efflux increased, there is no clear consensus explaining its cause and effect relation at present. However,
ischemia/reperfusion-induced coronary
hyperemia is believed to be mostly attributed to released
adenosine, and it has been proven that
adenosine attenuates the severity of
ischemia due to its coronary vasodilatory action. The beneficial effects of
adenosine during
ischemia/reperfusion processes do not seem simple. This is because
myocardial ischemia and
reperfusion injury is caused by 1) activated leukocytes and platelets, 2)
ATP depletion and
calcium overload of myocardium, and 3)
catecholamine release from the presynaptic nerves as well as 4) the impaired coronary circulation. Intriguingly
adenosine attenuates all of these deleterious actions and thereby attenuates
ischemia/reperfusion injury. Indeed,
adenosine attenuates the severity of contractile dysfunction (
myocardial stunning) and limits the
infarct size. Thus, administration of
adenosine or potentiators of
adenosine production in the ischemic myocardium may be beneficial for the attenuation of ischemic and
reperfusion injuries, although further clinical investigations are necessary.