Hypoxic pulmonary vasoconstriction is impaired in rats with nitrofen-induced congenital diaphragmatic hernia.
BACKGROUND
Pulmonary hypertension and persistent fetal circulation contribute to the high mortality rate associated with congenital diaphragmatic hernia (CDH). Morphological alterations of the pulmonary vasculature in infants with CDH are thought to contribute to exaggerated vasoconstrictor responses to normal vasoconstrictor stimuli. In the pulmonary circulation, hypoxia is a potent vasoconstrictor. Under pathological conditions, hypoxia-induced vasoconstriction may contribute to the development of pulmonary hypertension.


METHODS
The authors have used the nitrofen-induced model of congenital diaphragmatic hernia in rats to investigate the magnitude of the hypoxic vasoconstrictor response. Congenital diaphragmatic hernias were induced in fetal rats by feeding nitrofen (2,4-dichlorophenyl-p-nitrophenyl ether) to pregnant Sprague-Dawley rats at midgestation. Hypoxia-induced vasoconstriction was measured in isolated, perfused third-generation pulmonary arterioles from normal rats and from rats with nitrofen-induced CDH.


RESULTS
The hypoxic vasoconstrictor response was significantly blunted in the pulmonary arterioles of fetal rats with nitrofen-induced (2% +/- 1% vasoconstriction), as compared with the responses observed in normal fetal rats (15% +/- 3% vasoconstriction, P = .004).


CONCLUSIONS
Blunting of the hypoxic pulmonary vasoconstrictor response may contribute to ventilation-perfusion mismatching in infants with CDH.
Department of Surgery, Yale University School of Medicine, New Haven, CT 06520, USA.
M A
MA
Newell
M
M
Au-Fliegner
C P
CP
Coppola
J R
JR
Gosche
D000818:Animals; D001160:Arterioles / Q000502:physiology*; D004195:Disease Models, Animal; D005260:Female; D005333:Fetus / Q000502:physiology; D006540:Herbicides; D006548:Hernia, Diaphragmatic / Q000139:chemically induced / Q000503:physiopathology; D065630:Hernias, Diaphragmatic, Congenital; D000860:Hypoxia; D010647:Phenyl Ethers; D011247:Pregnancy; D011652:Pulmonary Circulation / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014661:Vasoconstriction / Q000502:physiology*
D006540:Herbicides; D010647:Phenyl Ethers; C007350:nitrofen