The roles of adenosine and related substances in exercise hyperaemia

The role of adenosine in exercise hyperaemia has been controversial. Accumulating evidence now demonstrates that adenosine is released into the venous efflux of exercising muscle and that adenosine is responsible for 20-40% of the maintained phase of the muscle vasodilatation that accompanies submaximal and maximal contractions. This adenosine is mainly generated from AMP that is released from the skeletal muscle fibres and dephosphorylated by ecto 5'nucleotidase bound to the sarcolemma. During exercise, the concentration of ecto 5'nucleotidase may be increased by translocation from the cytosol, while release of AMP and affinity of ecto 5'nucleotidase for AMP are increased by acidosis. The adenosine so formed, acts on extraluminal A(2A) receptors on the vascular smooth muscle. In addition, ATP is released from red blood cells into the plasma during exercise, in association with the unloading of O(2) from haemoglobin, while ATP and adenosine may be released from endothelium as a consequence of local hypoxia. It is unlikely that this intraluminal ATP, or adenosine, contributes significantly to exercise hyperaemia, for muscle vasodilatation induced by intraluminal ATP or adenosine is strongly nitric oxide dependent, while vasodilatation induced by adenosine in hypoxia is mediated by A(1) receptors. Neither is a recognized feature of exercise hyperaemia.