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Impaired voltage gated potassium channel responses in a fetal lamb model of persistent pulmonary hypertension of the newborn. Pediatr Res 2009 Sep;66(3):289-94

Date

06/23/2009

Pubmed ID

19542906

Pubmed Central ID

PMC3749926

DOI

10.1203/PDR.0b013e3181b1bc89

Abstract

We investigated the hypothesis that oxidative stress in persistent pulmonary hypertension of the newborn (PPHN) impairs voltage gated potassium (Kv) channel function. We induced PPHN in fetal lambs by prenatal ligation of ductus arteriosus; controls had sham ligation. We studied changes in the tone of pulmonary artery (PA) rings and Kv channel current of freshly isolated PA smooth muscle cells (PASMC) using standard techniques. 4-Aminopyridine (4-AP), a Kv channel antagonist, induced dose-dependent constriction of control PA rings; this response was attenuated in PPHN pulmonary arteries. Exogenous superoxide and peroxynitrite inhibited the response to 4-AP in control rings. Tiron, a superoxide scavenger, improved the response to 4-AP in PPHN rings. 4-AP inhibited the NOS-independent relaxation response to ATP in control PA rings. Relaxation response to ATP was blunted in PPHN rings and was improved by NOS antagonist, N-nitro-L-arginine methyl ester (L-NAME). 4-AP attenuated this response in L-NAME-treated PPHN rings. Exogenous superoxide suppressed 4-AP sensitive Kv current in control PASMC. Kv channel current was attenuated in cells from PPHN lambs and was restored by tiron. Oxidative stress impairs Kv channel function in PPHN. Superoxide scavengers may improve pulmonary vasodilation in PPHN in part by restoring Kv channel function.

Author List

Konduri GG, Bakhutashvili I, Eis A, Gauthier KM

Author

Girija Ganesh Konduri MD Chief, Professor in the Pediatrics department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

1,2-Dihydroxybenzene-3,5-Disulfonic Acid Disodium Salt
4-Aminopyridine
Adenosine Triphosphate
Animals
Animals, Newborn
Cells, Cultured
Female
Fetus
Free Radical Scavengers
Humans
Infant, Newborn
Myocytes, Smooth Muscle
Patch-Clamp Techniques
Persistent Fetal Circulation Syndrome
Potassium Channels, Voltage-Gated
Pregnancy
Pulmonary Artery
Reactive Oxygen Species
Sheep
Superoxide Dismutase
jenkins-FCD Prod-478 d1509cf07a111124a2d122fd3df854cc0b993c00