Role of adenosine triphosphate and adenosine in oxygen-induced pulmonary vasodilation in fetal lambs
Konduri, G.G.; Gervasio, C.T.; Theodorou, A.A.
Pediatric Research 33(5): 533-539
ISSN/ISBN: 0031-3998 PMID: 8511029 DOI: 10.1203/00006450-199305000-00022
We investigated the hypothesis that purine nucleotides, ATP and adenosine, mediate the pulmonary vasodilation that occurs at birth in response to an increase in arterial O-2 pressure (PaO-2). We studied 20 fetal lambs 1 to 3 d after placement of intravascular catheters and a flow transducer around left pulmonary artery. In 16 lambs, we investigated the effects of 1) an increase in fetal PaO-2 on ATP levels in pulmonary circulation and 2) 8-phenyltheophylline (8-PT) and cibacron blue, antagonists of receptors for adenosine and ATP, on pulmonary vasodilation caused by increased PaO-2. In four other lambs, we investigated the specificity of 8-PT and cibacron blue for purine receptors by investigating their effects on pulmonary vasodilation caused by acetylcholine, bradykinin, and nitroprusside. The fetal PaO-2 increased by 7 +- 2 during administration of 100% O-2 to the pregnant ewe, resulting in a 3-fold decrease in PVR and increase in pulmonary blood flow. Blood and plasma concentrations of ATP in fetal pulmonary artery and left atrium increased significantly during the increase in fetal PaO-2. 8-PT and cibacron blue caused increases in baseline pulmonary and systemic vascular pressures and pulmonary vascular resistance and inhibited the pulmonary vasodilation caused by O-2. 8-PT and cibacron blue did not alter the pulmonary vascular effects of acetylcholine, bradykinin, and nitroprusside. An increase in baseline pulmonary vascular resistance caused by infusion of U46619 (in four lambs) did not alter the pulmonary vasodilation caused by O-2. In summary, O-2-induced pulmonary vasodilation is accompanied by increased ATP levels in pulmonary circulation and is attenuated by antagonists of purine receptors. Adenosine and ATP are important mediators of O-2-induced pulmonary vasodilation in fetal lambs.