• A Mark Evans, D Grahame Hardie, Chris Peers, and Amira Mahmoud.
• Centre for Integrative Physiology, College of Medicine and Veterinary Medicine, University of Edinburgh, Edinburgh, UK. mark.evans@ed.ac.uk
• Curr Opin Anaesthesiol. 2011 Feb 1; 24 (1): 132013-20.

Purpose Of ReviewHypoxic pulmonary vasoconstriction (HPV) is driven by the intrinsic response to hypoxia of pulmonary arterial smooth muscle and endothelial cells. These are representatives of a group of specialized O2-sensing cells, defined by their acute sensitivity to relatively small changes in pO2, which have evolved to modulate respiratory and circulatory function in order to maintain O2 supply within physiological limits. The aim of this article is to discuss recent investigations into the mechanism(s) of hypoxia-response coupling and, in light of these, provide a critical assessment of current working hypotheses.Recent FindingsUpon exposure to hypoxia state-of-the-art technologies have now confirmed that mitochondrial oxidative phosphorylation is inhibited in all O2-sensing cells, including pulmonary arterial smooth muscle cells. Thereafter, evidence has been presented to indicate a role as principal effector for the 'gasotransmitters' carbon monoxide and hydrogen sulphide, reactive oxygen species or, in marked contrast, reduced cellular redox couples. Considering recent evidence in favour and against these proposals we suggest that an alternative mechanism may be key, namely the activation of adenosine monophosphate-activated protein kinase consequent to inhibition of mitochondrial oxidative phosphorylation.SummaryHPV supports ventilation-perfusion matching in the lung by diverting blood flow away from oxygen-deprived areas towards regions rich in O2. However, in diseases such as emphysema and cystic fibrosis, widespread HPV leads to hypoxic pulmonary hypertension and ultimately right heart failure. Determining the precise mechanism(s) that underpins hypoxia-response coupling will therefore advance understanding of the fundamental processes contributing to related pathophysiology and provide for improved therapeutics.

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