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
06/23/2009Pubmed ID
19542906Pubmed Central ID
PMC3749926DOI
10.1203/PDR.0b013e3181b1bc89Abstract
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 KMAuthor
Girija Ganesh Konduri MD Chief, Professor in the Pediatrics department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
1,2-Dihydroxybenzene-3,5-Disulfonic Acid Disodium Salt4-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
