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Archives of Disease in Childhood. Fetal and Neonatal Edition logoLink to Archives of Disease in Childhood. Fetal and Neonatal Edition
. 1997 Jul;77(1):F16–F22. doi: 10.1136/fn.77.1.f16

Endothelial nitric oxide synthase in hypoxic newborn porcine pulmonary vessels

A Hislop, D Springall, H Oliveira, J Pollock, J Polak, S Haworth
PMCID: PMC1720668  PMID: 9279177

Abstract

AIMS—To determine if the failure of neonatal pulmonary arteries to dilate is due to a lack of nitric oxide synthase (NOS).
METHODS—A monoclonal antibody to endothelial NOS was used to demonstrate the distribution and density of NOS in the developing porcine lung after a period in hypobaric hypoxia. Newborn piglets were made hypertensive by exposure to hypobaric hypoxia (50.8 kPa) from < 5 minutes of age to 2.5 days of age, 3-6 days of age or 14-17 days of age. A semiquantitative scoring system was used to assess the distribution of endothelial NOS by light microscopy.
RESULTS—NOS was present in the arteries in all hypoxic animals. However, hypoxia from birth caused a reduction in NOS compared with those lungs normal at birth and those normal at 3 days. Hypoxia from 3-6 days led to a high density of NOS compared with normal lungs at 6 days. Hypoxia from 14-17 days had little effect on the amount of NOS. On recovery in room air after exposure to hypoxia from birth there was a transient increase in endothelial NOS after three days of recovery, mirroring that seen at three days in normal animals.
CONCLUSIONS—Suppression of NOS production in the first few days of life may contribute to pulmonary hypertension in neonates.

 Keywords: pulmonary circulation; nitric oxide synthase; hypoxia; endothelium; piglets

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Figure 1  .

Figure 1  

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Mean (SD) percentage of arteries at bronchiolar level containing no endothelial NOS, containing up to 50%, or 51-100% in hypoxic and control piglets. *P<0.05 compared with controls of the same age.

Figure 2  .

Figure 2  

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NOS score (SD) for control and hypoxic animals in arteries at the level of the bronchioli, terminal bronchi, respiratory bronchioli, alveolar ducts, and alveoli. *P<0.05 compared with control 3 day olds; +P<0.05 compared with control 6 day olds.

Figure 3  .

Figure 3  

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NOS score (SD) for control (C), hypoxic (H), and recovery (R) animals at each arterial level in 0-2.5 day hypoxic group. *P<0.05 compared with control 3 day olds; +P<0.05 compared with 2.5 day hypoxic animals.

Figure 4  .

Figure 4  

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NOS score for control (C), hypoxic (H), and recovery (R) animals at respiratory bronchiolar level in (A) 3-6 day hypoxic group and in (B) 14-17 day hypoxic group. *P<0.05 compared with 6 day old controls; +P<0.05 compared with 6 day hypoxia.

Figure 5  .

Figure 5  

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Mean (SD) NOS score for the three hypoxic groups. *P<0.05 compared with controls of the same age; +P<0.05 compared with hypoxia.

Selected References

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