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Am J Physiol Lung Cell Mol Physiol 284: L489-L500, 2003. First published November 8, 2002; doi:10.1152/ajplung.00246.2002
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Vol. 284, Issue 3, L489-L500, March 2003

Exhaled NO is reduced at an early stage of hypoxia-induced pulmonary hypertension in newborn piglets

Joyce E. Turley1, Leif D. Nelin2, Mark R. Kaplowitz3, Yongmei Zhang3, and Candice D. Fike3

1 Department of Pediatrics, Medical College of Wisconsin, Milwaukee, Wisconsin 53226; 2 University of New Mexico School of Medicine, Albuquerque, New Mexico 87131; and 3 Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157

Altered nitric oxide (NO) production could contribute to the pathogenesis of hypoxia-induced pulmonary hypertension. To determine whether parameters of lung NO are altered at an early stage of hypoxia-induced pulmonary hypertension, newborn piglets were exposed to room air (control, n = 21) or 10% O2 (hypoxia, n = 19) for 3-4 days. Some lungs were isolated and perfused for measurement of exhaled NO output and the perfusate accumulation of nitrite and nitrate (NOx-), the stable metabolites of NO. Pulmonary arteries (20-600-µm diameter) and their accompanying airways were dissected from other lungs and incubated for NOx- determination. Abundances of the nitric oxide synthase (NOS) isoforms endothelial NOS and neural NOS were assessed in homogenates of PAs and airways. The perfusate NOx- accumulation was similar, whereas exhaled NO output was lower for isolated lungs of hypoxic, compared with control, piglets. The incubation solution NOx- did not differ between pulmonary arteries (PAs) of the two groups but was lower for airways of hypoxic, compared with control, piglets. Abundances of both eNOS and nNOS proteins were similar for PA homogenates from the two groups of piglets but were increased in airway homogenates of hypoxic compared with controls. The NO pathway is altered in airways, but not in PAs, at an early stage of hypoxia-induced pulmonary hypertension in newborn piglets.

nitric oxide synthase isoforms; pulmonary vascular nitric oxide; airway nitric oxide; chronic hypoxia


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