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1 Department of Anesthesiology, Justus-Liebig-University, Giessen, Germany; VA Medical Center, Minneapolis, Minnesota, USA
2 VA Medical Center, Minneapolis, Minnesota, USA
3 Department of Medicine, University of Minnesota, Minneapolis, Minnesota, USA
4 Scientist, VA Medical Center, Minneapolis, Minnesota, USA
5 Division of Pulmonary and Critical Care, Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota, USA
6 Department of Medicine and Physiology, University of Minnesota, Minneapolis, Minnesota, USA; VA Medical Center, Minneapolis, Minnesota, USA
* To whom correspondence should be addressed. E-mail: weirx002{at}umn.edu.
At birth, associated with the rise in oxygen tension, the pulmonary arteries (PA) dilate and the ductus arteriosu (DA) constricts. Both PA and DA constrict with vasoconstrictors and dilate with vasodilators. They only respond in a contrary manner to changes in oxygen tension. We have hypothesized that the effects of changes in oxygen are mediated by changes in redox status. Consequently, we tested whether a reducing agent dithiothreitol (DTT), and an oxidizing agent, dithionitrobenzoicacid (DTNB) would have opposite effects on a major oxygen signalling pathway in the PA and DA smooth muscle cells (SMCs); the sequence of change in potassium current (Ik), membrane potential, cytosolic calcium and vessel tone. Under normoxic conditions DTT constricted adult and fetal resistance PA rings, while in DA rings DTT acted as a potent vasodilator. In normoxia voltage clamp measurements showed inhibition of Ik by DTT in PASMCs and in contrast, activation in DASMCs. Consequently, DTT depolarized the fetal and adult PASMCs and hyperpolarized DASMCs. Intracellular [Ca2+] was increased by DTT in fetal and adult PASMCs and decreased in DASMCs. Under hypoxic conditions the oxidizing agent DTNB constricted DA rings and caused vasodilatation in fetal PA rings. DTNB inhibited Ik and depolarized the cell membrane in DASMCs. In contrast, activation of Ik and hyperpolarization were seen in PASMCs. Thus, the same redox signal can elicit opposite effects on potassium current, membrane potential, cytosolic calcium and vascular tone in the resistance PA and in the DA. These observations support the concept that redox changes could signal the opposite effects of oxygen in the PA and DA.
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