[Regulation of coronary circulation by adenosine]

The close coupling between energy expenditure and coronary blood flow has led very early on to the hypothesis, that metabolic factors form the essential link between metabolism and flow. Adenosine has been postulated to be an important mediator since this nucleoside is derived from ATP, readily can permeate through cell membranes and constitutes a potent vasodilator. Several animal studies, mainly performed in the 70ies, demonstrate a close correlation between coronary blood flow and adenosine without proving a causal relationship. More recent studies have concentrated on the cellular and molecular conditions which can be expected to cause an enhanced formation of adenosine. These studies revealed: 1. The free concentration of cytosolic ADP, as measured by NMR-spectroscopy, and the formation and release of adenosine do not measurably increase with elevated workload as long as the oxygen supply is adequate. The relation between free AMP and adenosine is more complex than previously assumed. There is a metabolic cycle between the two metabolites which functions to potentiate adenosine formation with only minor changes in AMP. 2. The coronary endothelium constitutes an important metabolic barrier for adenosine. It also can form adenosine and can liberate ATP which then act on endothelial A2- and P2-receptors, respectively. The relevance of the interrelationship between ATP-receptors, ecto-adenine-nucleotide-cascade and adenosine-receptors is presently only incompletely understood. In functional terms the data in the literature suggest that adenosine is not important for the setting of basal coronary blood flow. Mediators such as NO and endothelin may be more important under these circumstances. Adenosine, however, appears to play an important role under pathophysiological conditions when oxygen supply becomes limiting such as during hypoxia/ischemia, with coronary stenosis and reduced coronary flow reserve.