In response to the increase in oxygen tension at birth, the resistance pulmonary arteries dilate, while the ductus arteriosus constricts. Although modulated by the endothelium, these opposite responses are intrinsic to the vascular smooth muscle. While still controversial, it seems likely that during normoxia the production of reactive oxygen species (ROS) increases and the smooth muscle cell cytoplasm is more oxidized in both pulmonary arteries and ductus, compared to hypoxia. However, the effect of changes in the endogenous redox status or the addition of a redox agent, oxidizing or reducing, is exactly opposite in the two vessels. A reducing agent, dithiothreitol, like hypoxia, in the pulmonary artery will inhibit potassium current, cause depolarization, increase cytosolic calcium and lead to contraction. Responses to dithiothreitol in the ductus are opposite and removal of endogenous H2O2 by intracellular catalase in the ductus increases potassium current. Oxygen sensing in both vessels is probably mediated by redox effects on both calcium influx and calcium release from the sarcoplasmic reticulum (SR).
Bibliographical noteFunding Information:
E. Kenneth Weir is supported by general medical research funds from the US Department of Veterans Affairs and NIH (ROI-HL 65322-01A1). The authors appreciate the intellectual contributions of Stephen L. Archer, MD and Douglas A. Peterson, MD, PhD to the concepts developed in this paper.
- Endothelium, pulmonary
- Oxygen, sensing in pulmonary vessels
- Pulmonary vasculature, oxygen sensing
- Redox state, pulmonary vessels
- Smooth muscle, pulmonary vessels