Role of oxidative phosphorylation and ATP release in mediating birth-related pulmonary vasodilation in fetal lambs.
We investigated the hypothesis that birth-related pulmonary vasodilation is mediated in part by an increase in oxidative phosphorylation and ATP release in response to oxygen exposure at birth. Studies were done in fetal lambs to evaluate the independent effects of oxygen, lung distension alone, or lung distension accompanied by oxygenation and shear stress on fetal pulmonary blood flow and resistance and plasma ATP levels in the pulmonary artery. The effect of each intervention was evaluated in lambs assigned to one of three groups: control or pretreatment with 2,4-dinitrophenol or antimycin-A, inhibitors of oxidative phosphorylation. Exposure to oxygen alone or with lung distension was associated with increases in plasma ATP levels and pulmonary blood flow and a decrease in pulmonary vascular resistance. Plasma ATP levels did not change during lung distension alone. 2,4-Dinitrophenol and antimycin-A attenuated the pulmonary vasodilator response to oxygen but did not attenuate the response to lung distension alone. An increase in oxidative phosphorylation and ATP release during oxygen exposure may contribute to birth-related pulmonary vasodilation in fetal lambs.
Konduri
Girija G
GG
Department of Pediatrics and Cardiovascular Research Center, Medical College of Wisconsin, Milwaukee 53226, USA. Gkonduri@pol.net
Mattei
Janine
J
D000109:Acetylcholine / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D005260:Female; D007743:Labor, Obstetric / Q000502:physiology; D008168:Lung / Q000098:blood supply / Q000196:embryology / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D010085:Oxidative Phosphorylation; D010100:Oxygen / Q000097:blood / Q000494:pharmacology; D010396:Penicillamine / Q000031:analogs & derivatives* / Q000494:pharmacology; D011247:Pregnancy; D011652:Pulmonary Circulation / Q000187:drug effects / Q000502:physiology*; D012756:Sheep; D013314:Stress, Mechanical; D014655:Vascular Resistance / Q000187:drug effects / Q000502:physiology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*; D014665:Vasodilator Agents / Q000494:pharmacology
D020030:Nitric Oxide Donors; C110881:S-nitro-N-acetylpenicillamine; D014665:Vasodilator Agents; D000255:Adenosine Triphosphate; D010396:Penicillamine; D000109:Acetylcholine; D010100:Oxygen