Figure 7. Sources of extracellular ATP in the pulmonary artery vascular wall.

ATP release and signaling is an integral part of hypoxia-induced response in vascular wall. ATP can be released as a result of combined action of hypoxia, inflammation, fluid shear stress (changes in blood flow), injury, mechanical forces (SMC contractility), and sympathetic neurotransmission (release from perivascular nerve together with noradrenalin and neuropeptides). Importantly, vasa vasorum endothelial cell have been identified as an abundant source of extracellular ATP in pulmonary artery adventitia (118).

Collectively, within adventitial microenvironment, extracellular ATP acts in a synergistic manner with multiple pro-inflammatory and growth-promoting factors in hypoxic conditions. (SMC = smooth muscle cells; blood cells = erythrocytes, platelets, monocytes).