PT  - JOURNAL ARTICLE
AU  - Natascha Sommer
AU  - Ievgen Strielkov
AU  - Oleg Pak
AU  - Norbert Weissmann
TI  - Oxygen sensing and signal transduction in hypoxic pulmonary vasoconstriction
AID  - 10.1183/13993003.00945-2015
DP  - 2016 Jan 01
TA  - European Respiratory Journal
PG  - 288--303
VI  - 47
IP  - 1
4099  - http://erj.ersjournals.com/content/47/1/288.short
4100  - http://erj.ersjournals.com/content/47/1/288.full
SO  - Eur Respir J2016 Jan 01; 47
AB  - 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.ROS originating from mitochondria and/or NADPH oxidases may initiate HPV but exact signalling mechanisms are unclear http://ow.ly/SkaGC