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This Article Full Text Full Text (PDF) All Versions of this Article: 93/1/133    most recent expphysiol.2007.041236v1 Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Waypa, G. B. Articles by Schumacker, P. T. Search for Related Content PubMed PubMed Citation Articles by Waypa, G. B. Articles by Schumacker, P. T. Related Collections Symposia Papers

¹ Department of Pediatrics, Division of Neonatology, North-western University, Chicago, IL 60611, USA

Abstract

Hypoxic pulmonary vasoconstriction (HPV) becomes activated in response to alveolar hypoxia and, although the characteristics of HPV have been well described, the underlying mechanism of O₂ sensing which initiates the HPV response has not been fully established. Mitochondria have long been considered as a putative site of oxygen sensing because they consume O₂ and therefore represent the intracellular site with the lowest oxygen tension. However, two opposing theories have emerged regarding mitochondria-dependent O₂ sensing during hypoxia. One model suggests that there is a decrease in mitochondrial reactive oxygen species (ROS) levels during the transition from normoxia to hypoxia, resulting in the shift in cytosolic redox to a more reduced state. An alternative model proposes that hypoxia paradoxically increases mitochondrial ROS signalling in pulmonary arterial smooth muscle. Experimental resolution of the question of whether the mitochondrial ROS levels increase or decrease during hypoxia has been problematic owing to the technical limitations of the tools used to assess oxidant stress as well as the pharmacological agents used to inhibit the mitochondrial electron transport chain. However, recent developments in genetic techniques and redox-sensitive probes may allow us eventually to reach a consensus concerning the O₂ sensing mechanism underlying HPV.

(Received 30 October 2007; accepted after revision 9 November 2007; first published online 9 November 2007)
Corresponding author P. T. Schumacker: Department of Pediatrics, North-western University, Ward Building 12–191, 303 East Chicago Avenue, Chicago, IL 60611, USA. Email: p-schumacker{at}northwestern.edu

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