Nitrovasodilator responses in pulmonary arterioles from rats with nitrofen-induced congenital diaphragmatic hernia.
OBJECTIVE
Many infants with congenital diaphragmatic hernias (CDHs) experience persistent pulmonary hypertension that is refractory to treatment with inhaled nitric oxide (NO). We have examined the responses of isolated pulmonary arterioles from prenatal and postnatal rats with and without nitrofen (2,4-dichlorophenyl-p-nitrophenyl ether)-induced CDH to a variety of activators of the NO-cyclic guanosine monophosphate (cGMP) pathway.


METHODS
Right-sided CDH was induced in fetal rats by feeding nitrofen to pregnant rats on day 12 of gestation. Control rats were fed olive oil (vehicle). Third-generation pulmonary arterioles were isolated from the right lung of prenatal rats at term and from newborn rats within 8 hours after birth. Responses to increasing concentrations of sodium nitroprusside (SNP), atrial natriuretic peptide, or 8-bromo-cGMP were measured in pulmonary arterioles from control rats and from rats with nitrofen-induced CDH. Postnatal responses to 8-bromo-cGMP were also recorded in the presence of zaprinast, a type V phosphodiesterase inhibitor.


RESULTS
Pulmonary arterioles from prenatal rats did not dilate in response to SNP, atrial natriuretic peptide, or 8-bromo-cGMP. Vasodilatory responses of postnatal pulmonary arterioles from control rats to SNP and 8-bromo-cGMP were significantly greater than for arterioles from rats with CDH. Zaprinast pretreatment resulted in similar responses for postnatal CDH and control arterioles to 8-bromo-cGMP.


CONCLUSIONS
Postnatal pulmonary arterioles from CDH rats exhibit altered nitrovasodilator responsiveness, which may be due to rapid degradation of cGMP.
Vukcevic
Zoran
Z
The Division of Pediatric Surgery, Department of Surgery, Yale University School of Medicine, New Haven, CT 06520, USA.
Coppola
Christopher P
CP
Hults
Chris
C
Gosche
John R
JR
D000818:Animals; D001160:Arterioles / Q000187:drug effects* / Q000502:physiology; D009320:Atrial Natriuretic Factor / Q000494:pharmacology; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D004195:Disease Models, Animal; D006548:Hernia, Diaphragmatic / Q000150:complications / Q000503:physiopathology; D065630:Hernias, Diaphragmatic, Congenital; D006976:Hypertension, Pulmonary / Q000188:drug therapy / Q000503:physiopathology; D008168:Lung / Q000098:blood supply; D009569:Nitric Oxide / Q000494:pharmacology*; D009599:Nitroprusside / Q000494:pharmacology; D010575:Pesticides; D010647:Phenyl Ethers; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D011688:Purinones / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology
D010575:Pesticides; D010647:Phenyl Ethers; D010726:Phosphodiesterase Inhibitors; D011688:Purinones; D014665:Vasodilator Agents; D009599:Nitroprusside; C016276:8-bromocyclic GMP; D009569:Nitric Oxide; D009320:Atrial Natriuretic Factor; C011145:zaprinast; D006152:Cyclic GMP; C007350:nitrofen