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Am J Physiol Lung Cell Mol Physiol 274: L517-L526, 1998;
1040-0605/98 $5.00
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Vol. 274, Issue 4, L517-L526, April 1998

Chronic hypoxia decreases nitric oxide production and endothelial nitric oxide synthase in newborn pig lungs

Candice D. Fike, Mark R. Kaplowitz, Carol J. Thomas, and Leif D. Nelin

Department of Pediatrics, Medical College of Wisconsin, Milwaukee 53226; and Research Services, Zablocki Veterans Affairs Medical Center, Milwaukee, Wisconsin 53295

To examine the effect of chronic hypoxia on nitric oxide (NO) production and the amount of the endothelial isoform of nitric oxide synthase (eNOS) in lungs of newborn piglets, studies were performed using 1- to 3-day-old piglets raised in room air (control) or 10% O2 (chronic hypoxia) for 10-12 days. Exhaled NO output and plasma nitrites and nitrates (collectively termed NO<SUP>−</SUP><SUB>x</SUB>) were measured in anesthetized animals. NO<SUP>−</SUP><SUB>x</SUB> concentrations were measured in the perfusate of isolated lungs. eNOS amounts were assessed in whole lung homogenates. In the intact piglets, exhaled NO outputs and plasma NO<SUP>−</SUP><SUB>x</SUB> were lower in the chronically hypoxic (exhaled NO output = 0.2 ± 0.1 nmol/min; plasma NO<SUP>−</SUP><SUB>x</SUB> = 10.3 ± 3.7 nmol/ml) than in control animals (exhaled NO output = 0.8 ± 0.2 nmol/min; plasma NO<SUP>−</SUP><SUB>x</SUB> = 22.3 ± 4.3 nmol/ml). In perfused lungs, the perfusate accumulation of NO<SUP>−</SUP><SUB>x</SUB> was lower in chronic hypoxia (1.0 ± 0.3 nmol/min) than in control (2.6 ± 0.6 nmol/min) piglets. The amount of whole lung homogenate eNOS from the chronic hypoxia piglets was 40 ± 8% less than that from the control piglets. The reduced NO production observed in anesthetized animals or perfused lungs of chronically hypoxic newborn piglets is consistent with the finding of reduced lung eNOS protein amounts. Decreased NO production might contribute to the development of chronic hypoxia-induced pulmonary hypertension in newborns.

isolated perfused lungs; neonatal pulmonary hypertension; plasma levels


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