Impaired voltage gated potassium channel responses in a fetal lamb model of persistent pulmonary hypertension of the newborn.

Full 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 information

Author/s: Konduri, Girija G (GG); Bakhutashvili, Ivane (I); Eis, Annie (A); Gauthier, Kathryn M (KM);

Affiliation: Department of Pediatrics, Medical College of Wisconsin and Zablocki VA Medical Center, Milwaukee, Wisconsin 53226, USA. gkonduri(-atsign-)mcw.edu

Grants: R01 HL 57268 (Agency:NHLBI NIH HHS)

Journal and publication information

Publication Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't

Journal: Pediatric research (Pediatr Res), published in United States. (Language: eng)

Reference: 2009-Sep; vol 66 (issue 3) : pp 289-94

Dates: Created 2009/08/20; Completed 2009/10/27;

PMID: 19542906, status: MEDLINE (last retrieval date: 10/27/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Associated Chemicals: Free Radical Scavengers (0) ; Potassium Channels, Voltage-Gated (0) ; Reactive Oxygen Species (0) ; 1,2-Dihydroxybenzene-3,5-Disulfonic Acid Disodium Salt (149-45-1) ; 4-Aminopyridine (504-24-5) ; Adenosine Triphosphate (56-65-5) ; Superoxide Dismutase (EC 1.15.1.1)

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