Oxygen sensing and signal transduction in hypoxic pulmonary vasoconstriction.
Hypoxic pulmonary vasoconstriction (HPV), also known as the von Euler-Liljestrand mechanism, is an essential response of the pulmonary vasculature to acute and sustained alveolar hypoxia. During local alveolar hypoxia, HPV matches perfusion to ventilation to maintain optimal arterial oxygenation. In contrast, during global alveolar hypoxia, HPV leads to pulmonary hypertension. The oxygen sensing and signal transduction machinery is located in the pulmonary arterial smooth muscle cells (PASMCs) of the pre-capillary vessels, albeit the physiological response may be modulated in vivo by the endothelium. While factors such as nitric oxide modulate HPV, reactive oxygen species (ROS) have been suggested to act as essential mediators in HPV. ROS may originate from mitochondria and/or NADPH oxidases but the exact oxygen sensing mechanisms, as well as the question of whether increased or decreased ROS cause HPV, are under debate. ROS may induce intracellular calcium increase and subsequent contraction of PASMCs via direct or indirect interactions with protein kinases, phospholipases, sarcoplasmic calcium channels, transient receptor potential channels, voltage-dependent potassium channels and L-type calcium channels, whose relevance may vary under different experimental conditions. Successful identification of factors regulating HPV may allow development of novel therapeutic approaches for conditions of disturbed HPV.
Excellence Cluster Cardiopulmonary System, University of Giessen Lung Center, German Center for Lung Research (DZL), Justus-Liebig-University, Giessen, Germany.
Natascha
N
Sommer
Excellence Cluster Cardiopulmonary System, University of Giessen Lung Center, German Center for Lung Research (DZL), Justus-Liebig-University, Giessen, Germany.
Ievgen
I
Strielkov
Excellence Cluster Cardiopulmonary System, University of Giessen Lung Center, German Center for Lung Research (DZL), Justus-Liebig-University, Giessen, Germany.
Oleg
O
Pak
Excellence Cluster Cardiopulmonary System, University of Giessen Lung Center, German Center for Lung Research (DZL), Justus-Liebig-University, Giessen, Germany Norbert.Weissmann@innere.med.uni-giessen.de.
Norbert
N
Weissmann
D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000378:metabolism; D020746:Calcium Channels, L-Type / Q000378:metabolism; D006801:Humans; D006976:Hypertension, Pulmonary / Q000378:metabolism* / Q000503:physiopathology; D000860:Hypoxia / Q000378:metabolism*; D008168:Lung / Q000098:blood supply / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism; D009119:Muscle Contraction; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000378:metabolism*; D019255:NADPH Oxidases / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism*; D024642:Potassium Channels, Voltage-Gated / Q000378:metabolism; D011651:Pulmonary Artery / Q000378:metabolism; D011652:Pulmonary Circulation / Q000502:physiology*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction; D050916:TRPV Cation Channels / Q000378:metabolism; D014661:Vasoconstriction / Q000502:physiology*; D014692:Ventilation-Perfusion Ratio
D015220:Calcium Channels; D020746:Calcium Channels, L-Type; D024642:Potassium Channels, Voltage-Gated; D017382:Reactive Oxygen Species; D050916:TRPV Cation Channels; D009569:Nitric Oxide; D019255:NADPH Oxidases; D010100:Oxygen; D002118:Calcium