Pulmonary endothelial nitric oxide production is developmentally regulated in the fetus and newborn.
To define the role of endothelial nitric oxide (NO) in developmental changes in pulmonary vascular resistance and oxygen responsiveness, we determined the ontogeny of endothelial NO production and of oxygen modulation of that process in pulmonary arteries from fetal and newborn lambs. NO production was assessed by measuring endothelium-dependent arterial guanosine 3',5'-cyclic monophosphate synthesis. Basal NO rose two-fold from late gestation to 1 wk of age and another 1.6-fold from 1 to 4 wk. Acetylcholine-stimulated NO also increased 1.6-fold from 1 to 4 wk. The maturational rise in NO was evident at high Po2 in vitro, and it was not modified by L-arginine. This suggests that the developmental increase may alternatively involve enhanced calcium-calmodulin-mediated mechanisms, increased expression of NO synthase, or greater availability of required cofactor(s). With an acute decline in Po2 in vitro from 680 to 150 or 40 mmHg, there was 50-88% attenuation of basal and acetylcholine-stimulated NO late in the third trimester and in the newborn but not early in the third trimester. Parallel studies of mesenteric endothelium revealed postnatal increases in basal and stimulated NO but no decline in NO at lower Po2. Ontogenic changes in endothelial NO production and in oxygen modulation of that process may be involved in the maturational decrease in vascular resistance and the development of oxygen responsiveness in the pulmonary circulation.
Shaul
P W
PW
Department of Pediatrics, University of Texas Southwestern Medical Center at Dallas 75235-9063.
Farrar
M A
MA
Magness
R R
RR
D000375:Aging / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn / Q000254:growth & development / Q000378:metabolism*; D001120:Arginine / Q000031:analogs & derivatives; D006152:Cyclic GMP / Q000378:metabolism; D005314:Embryonic and Fetal Development; D004730:Endothelium, Vascular / Q000196:embryology / Q000254:growth & development / Q000378:metabolism*; D005333:Fetus / Q000378:metabolism*; D066298:In Vitro Techniques; D009569:Nitric Oxide / Q000096:biosynthesis*; D010100:Oxygen / Q000502:physiology; D011651:Pulmonary Artery / Q000196:embryology / Q000254:growth & development / Q000378:metabolism*; D012756:Sheep
D009569:Nitric Oxide; D001120:Arginine; D006152:Cyclic GMP; D010100:Oxygen