Ontogeny of NO activity and response to inhaled NO in the developing ovine pulmonary circulation.
To determine maturation-related changes in nitric oxide (NO) activity in the developing pulmonary circulation, we studied the hemodynamic effects of endogenous NO inhibition under basal conditions in the premature ovine fetus and the response to birth-related stimuli and exogenous NO in 30 fetal sheep at three different gestational ages. At 0.95 term, pulmonary vasodilation during inhaled NO (20 parts per million) was equivalent to the dilator response to 100% O2, but at 0.86 term vasodilation during inhaled NO was greater than the dilator response to 100% O2 (P < 0.05). At 0.78 term, left pulmonary arterial flow (QLPA) did not increase with exposure to either NO or 100% O2. Intrapulmonary infusion of nitro-L-arginine (L-NA) increased basal pulmonary vascular resistance 38% in the premature fetus at 0.78 term. L-NA treatment decreased the ventilation-induced rise in QLPA by 60% compared with controls (P < 0.05). Inhaled NO but not 100% O2 increased QLPA after L-NA treatment to levels achieved with ventilation alone in the controls. We conclude that in the premature pulmonary circulation (0.78 term) 1) basal pulmonary vascular resistance is modulated by endogenous NO, 2) pulmonary vasodilation at birth is partly mediated by endogenous NO activity, and 3) inhaled NO causes potent vasodilation.
Department of Pediatrics, Children's Hospital, Denver, Colorado.
J P
JP
Kinsella
D D
DD
Ivy
S H
SH
Abman
D000280:Administration, Inhalation; D000704:Analysis of Variance; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D005314:Embryonic and Fetal Development; D005260:Female; D005865:Gestational Age; D006439:Hemodynamics; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000196:embryology / Q000502:physiology; D009569:Nitric Oxide / Q000008:administration & dosage / Q000378:metabolism* / Q000494:pharmacology*; D019335:Nitroarginine; D010100:Oxygen / Q000494:pharmacology; D011247:Pregnancy; D011651:Pulmonary Artery / Q000187:drug effects / Q000196:embryology / Q000502:physiology*; D011652:Pulmonary Circulation / Q000187:drug effects / Q000502:physiology*; D012039:Regional Blood Flow / Q000187:drug effects; D012756:Sheep; D014655:Vascular Resistance / Q000187:drug effects
D019335:Nitroarginine; D009569:Nitric Oxide; D001120:Arginine; D010100:Oxygen