Release of adenosine by hypoxic canine lung tissue and its possible role in pulmonary circulation.
Adenosine is a possible mediator of myocardial and skeletal muscle blood flow regulation. Whether adenosine plays a similar role in modulating the pulmonary pressor response to acute alveolar hypoxia is not known. Adenosine levels (nmol/g tissue) in lung in six dogs ventilated with 95% N2, and 5% CO2 for a period of 3 min increased nearly 10-fold. Inosine and hypoxanthine, adenosine enzymatic degradation products, sustained a 10- and 7-fold increase, respectively. These degradative products are mainly formed in the capillary endothelial cells that contain the degradative enzyme nucleoside phosphorylase as demonstrated by histochemical techniques. To determine the effect of ATP, ADP, AMP, and adenosine on the pulmonary circulation, the in situ left lower lobe of 10 dogs was perfused at either free flow or constant flow via its pulmonary artery. ATP and ADP increased lobar vascular resistance; AMP and adenosine decreased the resistance. During hypoxic ventilation, adenosine infusions (100 nmol/ml blood) entirely abolished the increase in vascular resistance that was due solely to hypoxia. Dipyridamole produced similar responses. These data indicate that adenosine is a pulmonary vasodilator and that it may modulate the pulmonary pressor response to acute alveolar hypoxia. The findings suggest that the use of adenosine or dipyridamole may be beneficial in patients with pathologic elevations of the pulmonary vascular resistance which are a result of an exaggerated pulmonary pressor response to hypoxia, as seen in high-altitude pulmonary edema or that following cerebral injury.
D000241:Adenosine / Q000378:metabolism / Q000502:physiology*; D000244:Adenosine Diphosphate / Q000378:metabolism; D000249:Adenosine Monophosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D004285:Dogs; D006168:Guinea Pigs; D006651:Histocytochemistry; D000860:Hypoxia / Q000378:metabolism*; D008168:Lung / Q000378:metabolism* / Q000502:physiology / Q000648:ultrastructure; D008854:Microscopy, Electron; D010765:Phosphorylase Phosphatase / Q000378:metabolism; D011652:Pulmonary Circulation; D051381:Rats; D014655:Vascular Resistance
D000249:Adenosine Monophosphate; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D010765:Phosphorylase Phosphatase; D000241:Adenosine