Selective pulmonary vasodilation by low-dose infusion of adenosine triphosphate in newborn lambs.
The systemic and pulmonary vascular effects of adenosine 5'-triphosphate (ATP) were investigated in 12 newborn lambs during normoxia and during alveolar hypoxia (10% oxygen, 5% carbon dioxide, and 85% nitrogen). Lambs had catheters in the descending aorta, main pulmonary artery, and were studied after a 3-day recovery. We infused ATP or an equal volume of saline solution (control) into the right atrial line in doses ranging from 0.01 to 2.5 mumol/kg per minute. In normoxic lambs, ATP caused a significant decrease in pulmonary vascular resistance in doses of 0.08 to 2.5 mumol/kg per minute, and in systemic vascular resistance in doses of 0.3 to 2.5 mumol/kg per minute. Infusion of ATP in hypoxic lambs caused decreases in pulmonary artery pressure and pulmonary vascular resistance in all the doses tested. Systemic vascular resistance decreased, and cardiac output and heart rate increased in doses greater than 0.3 mumol/kg per minute in hypoxic lambs during ATP infusion. The effects of ATP in hypoxic lambs were not blocked by propranolol, indomethacin, or theophylline. Plasma ATP levels in left atrial blood samples did not change significantly during the infusion of ATP. We conclude that ATP is a vasodilator in lambs, and its effects are specific for pulmonary circulation at doses of less than or equal to 0.15 mumol/kg per minute. The vasodilator effects of ATP appear to be independent of P1 purinergic and beta-adrenergic mechanisms, and of prostacyclin synthesis.
Konduri
G G
GG
Department of Pediatrics, Children's Hospital of Michigan, Detroit.
Woodard
L L
LL
D000255:Adenosine Triphosphate / Q000097:blood / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D000831:Animals, Newborn; D001794:Blood Pressure / Q000187:drug effects; D002245:Carbon Dioxide / Q000097:blood; D002302:Cardiac Output / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D006976:Hypertension, Pulmonary / Q000188:drug therapy / Q000209:etiology; D000860:Hypoxia / Q000150:complications; D007263:Infusions, Parenteral; D010100:Oxygen / Q000097:blood; D011651:Pulmonary Artery / Q000187:drug effects*; D012756:Sheep; D014655:Vascular Resistance / Q000187:drug effects*; D014664:Vasodilation / Q000187:drug effects*
D002245:Carbon Dioxide; D000255:Adenosine Triphosphate; D010100:Oxygen