Exhaled NO is reduced at an early stage of hypoxia-induced pulmonary hypertension in newborn piglets.
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% O(2) (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-microm 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.
Turley
Joyce E
JE
Department of Pediatrics, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA.
Nelin
Leif D
LD
Kaplowitz
Mark R
MR
Zhang
Yongmei
Y
Fike
Candice D
CD
D000818:Animals; D000831:Animals, Newborn; D001273:Atmosphere Exposure Chambers; D001784:Blood Gas Analysis; D001980:Bronchi / Q000378:metabolism; D006976:Hypertension, Pulmonary / Q000209:etiology / Q000378:metabolism*; D000860:Hypoxia / Q000150:complications / Q000378:metabolism*; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D008168:Lung / Q000166:cytology / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052248:Nitric Oxide Synthase Type I; D052250:Nitric Oxide Synthase Type III; D010477:Perfusion; D011651:Pulmonary Artery / Q000378:metabolism; D011659:Pulmonary Gas Exchange / Q000502:physiology*; D013552:Swine
D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; D052250:Nitric Oxide Synthase Type III