Dual control of local blood flow by purines

The potent and widespread vascular actions of purine nucleotides and nucleosides have long been recognized. A dual function for ATP in the regulation of vascular tone is considered. ATP acts as an excitatory cotransmitter with noradrenaline from sympathetic perivascular nerves, to cause vasoconstriction via P2X-purinoceptors located on vascular smooth muscle. In contrast, ATP can act via P2Y-purinoceptors located on vascular endothelial cells to release EDRF, which diffuses to the vascular smooth muscle and produces vasodilatation. The main source of intraluminal ATP is likely to be endothelial cells, and its release can be measured during conditions such as changes in flow and hypoxia, in amounts sufficient to activate endothelial P2Y-purinoceptors. In some vessels, ATP acts directly on P2Y-purinoceptors located in the vascular smooth muscle to produce vasodilatation; the possibility that the origins of this ATP are nonsympathetic purinergic or sensory-motor nerves is discussed. ATP can also be released during intravascular platelet aggregation and from intact and damaged vascular smooth muscle cells, and so may play a role in the complex physiological mechanisms controlling local vascular tone under normoxic conditions, during changes in blood flow and during vessel injury.