Neuronal nitric oxide synthase does not contribute to the modulation of pulmonary vascular tone in fetal lambs with congenital diaphragmatic hernia (nNOS in CDH lambs).
OBJECTIVE
The aim of this study was to determine the presence of the neuronal nitric oxide synthase (nNOS) in near full-term lambs with congenital diaphragmatic hernia (CDH) and its role in the modulation of pulmonary vascular basal tone.


METHODS
We surgically created diaphragmatic hernia on the 85th day of gestation. On the 135th, catheters were used to measure pulmonary pressure and blood flow. We tested the effects of 7-nitroindazole (7-NINA), a specific nNOS antagonist and of N-nitro-L-arginine (L-NNA), a nonspecific nitric oxide synthase antagonist. In vitro, we tested the effects of the same drugs on isolated pulmonary vessels. The presence of nNOS protein in the lungs was detected by Western blot analysis.


RESULTS
Neither 7-NINA nor L-NNA modified pulmonary vascular basal tone in vivo. After L-NNA injection, acetylcholine (ACh) did not decrease significantly pulmonary vascular resistance (PVR). In vitro, L-NNA increased the cholinergic contractile-response elicited by electric field stimulation (EFS) of vascular rings from lambs with diaphragmatic hernia.


CONCLUSIONS
We conclude that nNOS protein is present in the lungs and pulmonary artery of near full-term lamb fetuses with diaphragmatic hernia, but that it does not contribute to the reduction of pulmonary vascular tone at birth.
de Buys Roessingh
Anthony S
AS
Faculté de Médecine, Université Paris Descartes, EA 2511, Assistance Publique Hôpitaux de Paris, Service de Physiologie-Explorations Fonctionnelles, Hôpital Cochin, Paris, France. anthony.debuys-roessingh@chuv.ch
de Lagausie
Pascal
P
Ebrahimian
Taline
T
Ibrahima
Taline
T
Duong-Quy
Sy
S
Schneider
Jean-Christophe
JC
Huang
Xiao-Lin
XL
Mercier
Jean-Christophe
JC
Aigrain
Yves
Y
Boulanger
Chantal
C
Dinh-Xuan
Anh Tuan
AT
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D015153:Blotting, Western; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005333:Fetus / Q000187:drug effects / Q000201:enzymology; D005865:Gestational Age; D006339:Heart Rate / Q000187:drug effects; D006548:Hernia, Diaphragmatic / Q000201:enzymology / Q000503:physiopathology*; D065630:Hernias, Diaphragmatic, Congenital; D008168:Lung / Q000098:blood supply / Q000187:drug effects / Q000503:physiopathology*; D052248:Nitric Oxide Synthase Type I / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009924:Organ Culture Techniques; D011651:Pulmonary Artery / Q000187:drug effects / Q000201:enzymology / Q000503:physiopathology*; D011652:Pulmonary Circulation / Q000187:drug effects; D012756:Sheep; D014655:Vascular Resistance / Q000187:drug effects
D004791:Enzyme Inhibitors; D052248:Nitric Oxide Synthase Type I