Opposite effects of redox status on membrane potential, cytosolic calcium, and tone in pulmonary arteries and ductus arteriosus

• Published in: American journal of physiology. Lung cellular and molecular physiology 2004-01, Vol.286 (1), p.15-L22
• Main Authors: Olschewski, Andrea, Hong, Zhigang, Peterson, Douglas A, Nelson, Daniel P, Porter, Valerie A, Weir, E. Kenneth
• Format: Article
• Language: English
• Subjects: Animals; Calcium - metabolism; Calcium Channels - physiology; Cytosol - metabolism; Dithionitrobenzoic Acid - pharmacology; Dithiothreitol - pharmacology; Ductus Arteriosus - metabolism; Female; Fetus; Hypoxia - metabolism; In Vitro Techniques; Membrane Potentials - drug effects; Membrane Potentials - physiology; Oxidation-Reduction; Oxygen - metabolism; Pregnancy; Pulmonary Artery - metabolism; Pulmonary Circulation - physiology; Rabbits; Rats; Sulfhydryl Reagents - pharmacology; Vasoconstriction - drug effects; Vasoconstriction - physiology
• ISSN: 1040-0605; 1522-1504
• DOI: 10.1152/ajplung.00372.2002

1 Justus Liebig University, 35385 Giessen, Germany; 2 Minneapolis Veterans Affairs Medical Center; and 3 Department of Pediatrics, Division of Pulmonary and Critical Care, and 4 Department of Medicine, University of Minnesota, Minneapolis, Minnesota 55417 Submitted 1 November 2002 ; accepted in final form 24 June 2003 At birth, associated with the rise in oxygen tension, the pulmonary arteries (PA) dilate and the ductus arteriosus (DA) constricts. Both PA and DA constrict with vasoconstrictors and dilate with vasodilators. They respond in a contrary manner only to changes in oxygen tension. We hypothesized that the effects of changes in oxygen are mediated by changes in redox status. Consequently, we tested whether a reducing agent, DTT, and an oxidizing agent, dithionitrobenzoic acid (DTNB), would have opposite effects on a major oxygen signaling pathway in the PA and DA smooth muscle cells (SMCs), the sequence of change in potassium current ( I K ), membrane potential ( E m ), cytosolic calcium, and vessel tone. Under normoxic conditions, DTT constricted adult and fetal resistance PA rings, whereas in DA rings DTT acted as a potent vasodilator. In normoxia, voltage-clamp measurements showed inhibition of I K by DTT in PASMCs and, in contrast, activation in DASMCs. Consequently, DTT depolarized fetal and adult PASMCs and hyperpolarized DASMCs. [Ca 2+ ] i was increased by DTT in fetal and adult PASMCs and decreased in DASMCs. Under hypoxic conditions, DTNB constricted DA rings and caused vasodilatation in fetal PA rings. DTNB inhibited I K and depolarized the cell membrane in DASMCs. In contrast, activation of I K and hyperpolarization was seen in PASMCs. Thus the same redox signal can elicit opposite effects on I K , E m , cytosolic calcium, and vascular tone in resistance PA and the DA. These observations support the concept that redox changes could signal the opposite effects of oxygen in the PA and DA. hypoxia; potassium channels; resting membrane potential; pulmonary vasoconstriction Address for reprint requests and other correspondence: E. K. Weir, VA Medical Center (111 C), 1 Veterans Dr., Minneapolis, MN 55417 (E-mail: weirx002{at}umn.edu ).