Hypoxic pulmonary vasoconstriction.
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 tissues they supply. Physiologically, HPV contributes to ventilation-perfusion matching in the lung by diverting blood flow to oxygen-rich areas. However, when alveolar hypoxia is global, as in diseases such as emphysema and cystic fibrosis, HPV leads to HPH (hypoxic pulmonary hypertension) and right heart failure. HPV is driven by the intrinsic response to hypoxia of two different cell types, namely the pulmonary arterial smooth muscle and endothelial cells. These are representatives of a group of specialized cells, commonly referred to as oxygen-sensing cells, which are defined by their acute sensitivity to relatively small changes in PO(2) 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, mediates 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 endothelium, which leads to further constriction of the smooth muscle by increasing the sensitivity of the contractile apparatus to calcium.
A Mark
Evans
E
School of Biology, Bute Building, University of St Andrews, St Andrews, Fife KY16 9TS, U.K. ame3@st-and.ac.uk
D000818:Animals; D001158:Arteries / Q000473:pathology; D001692:Biological Transport; D002118:Calcium / Q000378:metabolism; D006801:Humans; D000860:Hypoxia; D008171:Lung Diseases / Q000175:diagnosis / Q000473:pathology*; D008954:Models, Biological; D009130:Muscle, Smooth / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000378:metabolism; D010084:Oxidation-Reduction; D010100:Oxygen / Q000378:metabolism; D011652:Pulmonary Circulation; D012519:Sarcoplasmic Reticulum / Q000378:metabolism; D014661:Vasoconstriction
D010100:Oxygen; D002118:Calcium