Chronic O2 exposure in the newborn rat results in decreased pulmonary arterial nitric oxide release and altered smooth muscle response to isoprostane.
Chronic oxygen exposure in the newborn rat results in lung isoprostane formation, which may contribute to the pulmonary hypertension evident in this animal model. The purpose of this study was to investigate the pulmonary arterial smooth muscle responses to 8-iso-prostaglandin F(2alpha) (8-iso-PGF(2a)) in newborn rats exposed to 60% O2 for 14 days. Because, in the adult rat, 8-iso-PGF(2alpha) may have a relaxant effect, mediated by nitric oxide (NO), we also sought to evaluate the pulmonary arterial NO synthase (NOS) protein content and NO release in the newborn exposed to chronic hyperoxia. Compared with air-exposed control animals, 8-iso-PGF(2a) induced a significantly greater force (P < 0.01) and reduced (P < 0.01) relaxation of precontracted pulmonary arteries in the 60% O2-treated animals. These changes were reproduced in control pulmonary arteries by NOS blockade by using NG-nitro-L-arginine methyl ester. Pulmonary arterial endothelial NOS was unaltered, but the inducible NOS protein content was significantly decreased (P < 0.01) in the experimental group. Pulmonary (P < 0.05) and aortic (P < 0.01) tissue ex vivo NO accumulation was significantly reduced in the 60% O2-treated animals. We speculate that impaired pulmonary vascular tissue NO metabolism after chronic O2 exposure potentiates 8-iso-PGF(2alpha)-induced vasoconstriction in the newborn rat, thus contributing to pulmonary hypertension.
Belik
J
J
Department of Paediatrics, Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada M5G 1X8. Jaques.Belik@SickKids.ca
Jankov
R P
RP
Pan
J
J
Yi
M
M
Chaudhry
I
I
Tanswell
A K
AK
D000818:Animals; D000831:Animals, Newborn; D002908:Chronic Disease; D015237:Dinoprost / Q000031:analogs & derivatives / Q000494:pharmacology; D005260:Female; D018496:Hyperoxia / Q000378:metabolism* / Q000503:physiopathology; D006976:Hypertension, Pulmonary / Q000378:metabolism* / Q000503:physiopathology; D028421:Isoprostanes / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D010100:Oxygen / Q000494:pharmacology; D011247:Pregnancy; D011651:Pulmonary Artery / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D028421:Isoprostanes; D014662:Vasoconstrictor Agents; C075750:8-epi-prostaglandin F2alpha; D009569:Nitric Oxide; D015237:Dinoprost; D019001:Nitric Oxide Synthase; D010100:Oxygen