Abstract
High mortality in newborn babies with congenital diaphragmatic hernia (CDH) is principally due to persistent pulmonary hypertension. ATP-dependent potassium (KATP) channels might modulate pulmonary vascular tone. We have assessed the effects of Pinacidil, a KATP channel opener, and glibenclamide (GLI), a KATP 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 KATP 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 μM) relaxed, precontracted arteries from lambs with and without CDH. GLI (10−5 μM) did not raise the basal tone of vessels. We conclude that activation of KATP 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.
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Abbreviations
- Ach:
-
acetylcholine
- Ao:
-
aorta
- CD:
-
congenital diaphragmatic hernia
- EDHF:
-
endothelium-derived hyperpolarizing factor
- EDNO:
-
endothelium-derived nitric oxide
- ET (-1):
-
endothelin (-1)
- GLI:
-
glibenclamide
- KATP:
-
ATP-dependent potassium
- LPA:
-
left pulmonary artery
- PAP:
-
pulmonary arterial pressure
- PVR:
-
pulmonary vascular resistance
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Acknowledgements
The authors are grateful to Virginie Hannecke for her histologic assistance and to Dr Jean-Christophe Schneider for his statistical help.
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This work was funded in part by grants from the Académie Nationale de Médecine [A.S.B.R.] France; from the Fondation de l'Avenir [P. de L.], France; from SmithKline Beecham Institute, 92731 Nanterre, France; from the Centre Hospitalier universitaire vaudois (CHUV), service de chirurgie pédiatrique, Lausanne, Switzerland [A.S.B.R.]; from the Fond Decker, CHUV, Switzerland [A.S.B.R.]; from Fidax S.A., Suisse [A.S.B.R.]. Pinacidil was kindly supplied by Leo Pharmaceutical Products Copenhagen, Denmark.
This work was presented at the 57th meeting of the French Association of Pediatric Surgeons, on 22nd September 2000, in Paris.
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de Buys Roessingh, A., de Lagausie, P., Barbet, JP. et al. Role of ATP-Dependent Potassium Channels in Pulmonary Vascular Tone of Fetal Lambs With Congenital Diaphragmatic Hernia. Pediatr Res 60, 537–542 (2006). https://doi.org/10.1203/01.pdr.0000242372.99285.72
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DOI: https://doi.org/10.1203/01.pdr.0000242372.99285.72
