Received October 30, 2007
Revised November 9, 2007
Accepted after revision November 9, 2007
O2 SENSING IN HYPOXIC PULMONARY VASOCONSTRICTION:
USING NEW TOOLS TO ANSWER AN AGE OLD QUESTION
Gregory B Waypa 1
Paul T. Schumacker 1*
1 Northwestern University
* To whom correspondence should be addressed. E-mail: p-schumacker{at}northwestern.edu.
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Abstract |
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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 mitochondrial-dependent O2 sensing during hypoxia. One model suggests that there is a decrease in mitochondrial reactive oxygen species (ROS) levels during 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 signaling in pulmonary arterial smooth muscle (PASMC). Experimental resolution of the question as to whether the mitochondrial ROS levels increase or decrease during hypoxia has been problematic due to the technical limitations of the tools used to assess oxidant stress as well as pharmacological agents used to inhibit the mitochondrial electron transport chain (ETC). However, recent developments in genetic techniques and redox-sensitive probes may allow us to one day reach a consensus as to the O2 sensing mechanism underlying HPV.
Key Words:
Hypoxia, Oxidation, Pulmonary circulation
