Antenatal dexamethasone administration inhibits smooth-muscle-cell DNA synthesis in pulmonary-arterial media in nitrofen-induced congenital diaphragmatic hernia in rats.
The aim of this study was to investigate the effect of antenatal glucocorticoid therapy on smooth-muscle-cell (SMC) DNA synthesis in the pulmonary arteries (PA) in a nitrofen-induced congenital diaphragmatic hernia (CDH) rat model following nitrofen administration on day 9.5 of gestation. Antenatal dexamethasone (DEX) was given intraperitoneally on days 18.5 and 19.5 of gestation. Bromodeoxyuridine (BrdU) was injected via a jugular vein into the dam 1 h before the fetuses were killed by cesarean section at term. The fetuses were divided into three groups: group I (n = 10): normal controls; group II (n = 10): nitrofen-induced CDH; group III (n = 10): nitrofen-induced CDH with antenatal DEX treatment. Immunostaining of the lungs with anti-BrdU antibody was obtained by a standard avidin-biotin complex method. The number of immunopositive cells in the PA media and adventitia were counted using an image analyzer and analyzed statistically. The number of BrdU-immunopositive cells in the media was significantly increased in group II (16.83 +/- 3.01) compared to groups I (9.16 +/- 2.20) and III (6.83 +/- 1.70) (P < 0.01). There was no significant difference between groups I and III. The number of BrdU-immunopositive cells in the adventitia was not significantly different between the three groups. Antenatal DEX treatment inhibits SMC DNA synthesis in PA media in CDH lungs. This may be a possible mechanism by which antenatal DEX prevents structural PA changes in nitrofen-induced CDH in rats.
Taira
Y
Y
Children's Research Centre, Our Lady's Hospital for Sick Children, Crumlin, Dublin, Ireland.
Shima
H
H
Miyazaki
E
E
Ohshiro
K
K
Puri
P
P
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage*; D000963:Antimetabolites / Q000008:administration & dosage; D001973:Bromodeoxyuridine / Q000008:administration & dosage; D004247:DNA / Q000096:biosynthesis* / Q000187:drug effects*; D003907:Dexamethasone / Q000008:administration & dosage*; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D005260:Female; D006548:Hernia, Diaphragmatic / Q000139:chemically induced / Q000150:complications / Q000473:pathology / Q000517:prevention & control*; D065630:Hernias, Diaphragmatic, Congenital; D006976:Hypertension, Pulmonary / Q000209:etiology; D007150:Immunohistochemistry; D010647:Phenyl Ethers; D011247:Pregnancy; D011295:Prenatal Care / Q000379:methods*; D011651:Pulmonary Artery / Q000196:embryology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017540:Tunica Media / Q000196:embryology* / Q000648:ultrastructure*
D000893:Anti-Inflammatory Agents; D000963:Antimetabolites; D010647:Phenyl Ethers; D003907:Dexamethasone; D004247:DNA; D001973:Bromodeoxyuridine; C007350:nitrofen