Oxygen-induced vasodilation is blunted in pulmonary arterioles from fetal rats with nitrofen-induced congenital diaphragmatic hernia.
OBJECTIVE
Persistent pulmonary hypertension contributes to the high mortality rate associated with congenital diaphragmatic hernia (CDH). Oxygen is an important stimulus for pulmonary vasodilation in the perinatal period. The authors have investigated the responses of isolated pulmonary arterioles from fetal rats with and without CDH to an increase in oxygen tension.


METHODS
CDHs were induced in fetal rats by feeding nitrofen to timed-pregnant rats at midgestation. A third-generation pulmonary arteriole was isolated from the right lung at term. Isolated arterioles were pressurized at their "optimal distending pressure." Diameter changes in response to an increase in oxygen tension from 25 to 40 mm Hg ("hypoxic" conditions) to 90 to 150 mm Hg ("normoxic" conditions) were recorded for K(+) preconstricted arterioles from control rats, from rats with nitrofen-induced CDH, and from rats that were nitrofen exposed but did not have a CDH.


RESULTS
"Normoxic" exposure reversed the K(+) preconstriction in control arterioles by 124 +/- 26%. In contrast, arterioles from rats with nitrofen-induced CDH dilated significantly less than controls (20 +/- 15% of the K(+) preconstriction). The responses of arterioles from rats that were nitrofen exposed but did not get a CDH were not different (P >.05) from controls.


CONCLUSIONS
Oxygen-induced vasodilation is blunted in pulmonary arterioles from rats with nitrofen-induced CDH. Blunted oxygen-induced vasodilation may contribute to persistent pulmonary hypertension in CDH. J Pediatr Surg 36:593-597.
Pediatric Surgical Research Laboratory, Division of Pediatric Surgery, Department of Surgery, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520, USA..
C P
CP
Coppola
J R
JR
Gosche
D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D046508:Culture Techniques; D004195:Disease Models, Animal; D005260:Female; D006551:Hernia, Hiatal / Q000139:chemically induced / Q000150:complications* / Q000151:congenital / Q000503:physiopathology*; D006976:Hypertension, Pulmonary / Q000150:complications / Q000175:diagnosis; D010100:Oxygen / Q000494:pharmacology; D010647:Phenyl Ethers; D011247:Pregnancy; D011270:Pregnancy, Animal; D011336:Probability; D011651:Pulmonary Artery / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D014664:Vasodilation / Q000187:drug effects
D010647:Phenyl Ethers; C007350:nitrofen; D010100:Oxygen