Role of ATP-dependent potassium channels in pulmonary vascular tone of fetal lambs with congenital diaphragmatic hernia.
High mortality in newborn babies with congenital diaphragmatic hernia (CDH) is principally due to persistent pulmonary hypertension. ATP-dependent potassium (K(ATP)) channels might modulate pulmonary vascular tone. We have assessed the effects of Pinacidil, a K(ATP) channel opener, and glibenclamide (GLI), a K(ATP) channel blocker, in near full-term lambs with and without CDH. In vivo, pulmonary hemodynamics were assessed by means of pressure and blood flow catheters. In vitro, we used isolated pulmonary vessels and immunohistochemistry to detect the presence of K(ATP) channels in pulmonary tissue. In vivo, pinacidil (2 mg) significantly reduced pulmonary vascular resistance (PVR) in both controls and CDH animals. GLI (30 mg) significantly increased pulmonary arterial pressure (PAP) and PVR in control animals only. In vitro, pinacidil (10 microM) relaxed, precontracted arteries from lambs with and without CDH. GLI (10(-5) microM) did not raise the basal tone of vessels. We conclude that activation of K(ATP) channels could be of interest to reduce pulmonary vascular tone in fetal lambs with CDH, a condition often associated with persistent pulmonary hypertension of the newborn.
de Buys Roessingh
Anthony S
AS
Department of Pediatric Surgery, Robert Debré Hospital, Assistance Publique-Hôpitaux de Paris-Université Paris 7, 75019 Paris, France. anthony.debuys-roessingh@chuv.ch
de Lagausie
Pascal
P
Barbet
Jacques-Patrick
JP
Mercier
Jean-Christophe
JC
Aigrain
Yves
Y
Dinh-Xuan
Anh Tuan
AT
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D005260:Female; D005905:Glyburide / Q000494:pharmacology; D006548:Hernia, Diaphragmatic / Q000503:physiopathology; D065630:Hernias, Diaphragmatic, Congenital; D006976:Hypertension, Pulmonary; D008168:Lung / Q000033:anatomy & histology / Q000196:embryology / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism; D010656:Phenylephrine / Q000494:pharmacology; D020110:Pinacidil / Q000494:pharmacology*; D015221:Potassium Channels / Q000378:metabolism*; D011247:Pregnancy; D011652:Pulmonary Circulation / Q000187:drug effects*; D034561:Sheep, Domestic; D014655:Vascular Resistance / Q000187:drug effects*; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology*
D015221:Potassium Channels; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D010656:Phenylephrine; D020110:Pinacidil; D000255:Adenosine Triphosphate; D005905:Glyburide