Hypoxic pulmonary vasoconstriction: from molecular mechanisms to medicine.

Hypoxic pulmonary vasoconstriction: from molecular mechanisms to medicine. Chest. 2016 Sep 16; Authors: Dunham-Snary KJ, Danchen Wu, Sykes EA, Thakrar A, Parlow LR, Mewburn JD, Parlow JL, Archer SL Abstract Hypoxic pulmonary vasoconstriction (HPV) is a homeostatic mechanism that is intrinsic to the pulmonary vasculature. Intrapulmonary arteries constrict in response to alveolar hypoxia, diverting blood to better-oxygenated lung segments, thereby optimizing ventilation-perfusion matching and systemic oxygen delivery. In response to alveolar hypoxia, a mitochondrial sensor dynamically changes reactive oxygen species and redox couples in PASMC. This inhibits potassium channels, depolarizes PASMC, activates voltage-gated calcium channels, and increases cytosolic calcium, causing vasoconstriction. Sustained hypoxia activates rho kinase, reinforcing vasoconstriction, and HIF-1α, leading to adverse pulmonary vascular remodelling and pulmonary hypertension (PH). In the non-ventilated fetal lung, HPV diverts blood to the systemic vasculature. After birth, HPV commonly occurs as a localized homeostatic response to focal pneumonia or atelectasis that optimizes systemic PO2 without altering pulmonary artery pressure. In single-lung anesthesia, HPV reduces blood flow to the non-ventilated lung thereby facilitating thoracic surgery. At altitude, global hypoxia causes diffuse HPV, increases PA pressure and initiates PH. Exaggerated or heterogeneou...
Source: Chest - Category: Respiratory Medicine Authors: Tags: Chest Source Type: research