Developmental regulation of oxygen sensing and ion channels in the pulmonary vasculature.
The increase in oxygen tension occurring at birth causes sustained and progressive pulmonary vasodilation. The oxygen-induced perinatal pulmonary vasodilation depends on the production of nitric oxide (NO) from the pulmonary endothelium and activation of various K(+) channels in pulmonary artery smooth muscle cells. This chapter reviews a) the oxygen-sensing mechanism that stimulates endothelial NO production; b) how K(+) channels sense changes in oxygen tension; c) whether hypoxia-inducible factor-1alpha (HIF-1alpha), a well defined hypoxia-sensitive transcription factor in adult, contributes to the regulation of NO production and K(+) channel activation; and d) whether and how dysfunctional K(+) channels contribute to the development of pulmonary hypertension in the newborns.
Cornfield
David N
DN
Divisions of Pediatric Pulmonary, Allergy, and Critical Care Medicine, Stanford University Medical School Medicine, 770 Welch Road, Suite 350, Stanford, CA, 94305, USA. cornfield@stanford.edu
D005333:Fetus / Q000033:anatomy & histology / Q000502:physiology; D018507:Gene Expression Regulation, Developmental; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism; D007473:Ion Channels / Q000378:metabolism*; D007527:Isoenzymes / Q000378:metabolism; D008168:Lung / Q000098:blood supply / Q000254:growth & development / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000166:cytology; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism*; D026902:Potassium Channel Blockers / Q000378:metabolism; D011393:Procollagen-Proline Dioxygenase / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism; D012433:Ryanodine / Q000378:metabolism; D015534:Trans-Activators / Q000378:metabolism; D014664:Vasodilation / Q000502:physiology
D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D007473:Ion Channels; D007527:Isoenzymes; D026902:Potassium Channel Blockers; D012097:Repressor Proteins; D015534:Trans-Activators; D012433:Ryanodine; D011393:Procollagen-Proline Dioxygenase; D010100:Oxygen