In the pulmonary circulation, the ultimate role of liberated adenosine 5'-triphosphate (ATP) is to influence vascular tone. Extracellular ATP may be derived from sympathetic or purinergic nerves impinging on blood vessels, in addition to vascular endothelial cells, erythrocytes, thrombocytes and mast cells. Purinergic innervation is more marked on the arterial side than the venous, and produces vasoconstriction through P2X purinoceptors although there is a newly discovered non-P2X purinoceptor mediated vasoconstriction produced by ATP which remains to be characterized. Agonists as well as flow derived shear stress have been shown to release ATP from endothelial cells, which in turn act on either the same cell in an autoregulatory manner, or the ATP may travel short distances in the blood to act on endothelial cells downstream. Activation of endothelial P2Y purinoceptors by ATP produces nitric oxide release and vasodilation. There are also P2Y purinoceptors on pulmonary vascular smooth muscle, and it appears that the number of P2Y purinoceptors located on the smooth muscle is inversely proportional to vessel size. Unlike other sources of ATP, erythrocytes as well as mast cells are relatively mobile and the magnitude of their effect can change due to alterations in their number. Thrombocyte derived ATP can be released by episodes of hypoxia, and the P2T purinoceptor on thrombocytes may have an autoregulatory function. The P2Z purinoceptor is activated by ATP and has been shown to inhibit the activity of natural killer cells as well as macrophages in addition to producing degranulation of mast cells. It is likely that together with unique features of pulmonary vascular smooth muscle, a combination of purinoceptor mediated mechanisms contributes to the unusual characteristics of the pulmonary circulation. Such a varied and essential role of purinergic regulatory mechanisms in the pulmonary circulation makes purinoceptors sensible targets for therapeutic strategies.
Biomedical Reviews 1994; 3: 11-25.
Email this article (Login required) 
