© The Authors Journal compilation © 2007 Biochemical Society 5

HPV (hypoxic pulmonary vasoconstriction) is the critical and distinguishing characteristic of the arteries that feed the lung. In marked contrast, systemic arteries dilate in response to hypoxia to meet the metabolic demands of the tis-sues they supply. Physiologically, HPV contributes to ventilation–perfusion matching in the lung by diverting blood fl ow to oxygen-rich areas. However, when alveolar hypoxia is global, as in diseases such as emphysema and cystic fi brosis, HPV leads to HPH (hypoxic pulmonary hypertension) and right heart failure. HPV is driven by the intrinsic response to hypoxia of two dif-ferent cell types, namely the pulmonary arterial smooth muscle and endothe-lial cells. These are representatives of a group of specialized cells, commonly referred to as oxygen-sensing cells, which are defi ned by their acute sensitiv-ity to relatively small changes in PO2 and have evolved to monitor oxygen supply and alter respiratory and circulatory function, as well as the capacity of the blood to transport oxygen. Upon exposure to hypoxia, mitochondrial oxidative phosphorylation is inhibited in all such cells and this, in part, medi-ates cell activation. In the case of pulmonary arteries, constriction is triggered via: (i) calcium release from the smooth muscle sarcoplasmic reticulum and consequent store-depletion-activated calcium entry into the smooth muscle cells and, (ii) the modulation of transmitter release from the pulmonary artery 1To whom correspondence should be addressed (emai