Effects of birth-related stimuli on L-arginine-dependent pulmonary vasodilation in ovine fetus.
To determine the effects of birth-related stimuli on L-arginine-dependent vasodilation or nitric oxide (NO) activity in the perinatal lung, we studied the fetal pulmonary vascular effects of nitro-L-arginine (L-NA), a specific inhibitor of NO formation, during 1) mechanical ventilation without altering fetal blood gas tensions; 2) administration of high oxygen concentrations; and 3) increased flow or shear stress. In the first protocol, 13 late-gestation fetal lambs were ventilated with low fraction of inspired oxygen concentration (FIO2 less than or equal to 0.10) for 60 min after infusion of L-NA or saline into the left pulmonary artery (LPA). In control animals, LPA flow steadily increased during 60 min of ventilation. With L-NA treatment, the rise in flow and decrease in total pulmonary resistance (TPR) were reduced 67% (P less than 0.001 vs. control) and 28% (P less than 0.01 vs. control), respectively. Subsequent ventilation with high FIO2 (1.00) decreased mean pulmonary arterial pressure (PAP) in control but not in L-NA-treated animals. TPR remained fourfold greater in L-NA-treated animals than in control animals (P less than 0.001). In the second protocol, with partial compression of the ductus arteriosus, LPA flow increased 300% and TPR decreased 61% over 30 min. After L-NA treatment the rise in blood flow and decrease in TPR was markedly attenuated (P less than 0.001). We conclude that the perinatal pulmonary vasodilator response to ventilation without changing arterial oxygen tension and ventilation with increased oxygen tension are modulated by NO.(ABSTRACT TRUNCATED AT 250 WORDS)
Cornfield
D N
DN
Department of Pediatrics, Children's Hospital, Denver, Colorado.
Chatfield
B A
BA
McQueston
J A
JA
McMurtry
I F
IF
Abman
S H
SH
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology / Q000502:physiology*; D001794:Blood Pressure / Q000187:drug effects; D005260:Female; D005333:Fetus / Q000502:physiology*; D007743:Labor, Obstetric / Q000502:physiology*; D019335:Nitroarginine; D011247:Pregnancy; D011651:Pulmonary Artery / Q000502:physiology; D011652:Pulmonary Circulation / Q000187:drug effects; D012119:Respiration; D012756:Sheep; D014655:Vascular Resistance / Q000187:drug effects; D014664:Vasodilation
D019335:Nitroarginine; D001120:Arginine