Recent advances in oxygen sensing and signal transduction in hypoxic pulmonary vasoconstriction

J Appl Physiol (1985). 2017 Dec 1;123(6):1647-1656. doi: 10.1152/japplphysiol.00103.2017. Epub 2017 Jul 27.

Abstract

Hypoxic pulmonary vasoconstriction (HPV) is a physiological reaction, which adapts lung perfusion to regional ventilation and optimizes gas exchange. Impaired HPV may cause systemic hypoxemia, while generalized HPV contributes to the development of pulmonary hypertension. The triggering mechanisms underlying HPV are still not fully elucidated. Several hypotheses are currently under debate, including a possible decrease as well as an increase in reactive oxygen species as a triggering event. Recent findings suggest an increase in the production of reactive oxygen species in pulmonary artery smooth muscle cells by complex III of the mitochondrial electron transport chain and occurrence of oxygen sensing at complex IV. Other essential components are voltage-dependent potassium and possibly L-type, transient receptor potential channel 6, and transient receptor potential vanilloid 4 channels. The release of arachidonic acid metabolites appears also to be involved in HPV regulation. Further investigation of the HPV mechanisms will facilitate the development of novel therapeutic strategies for the treatment of HPV-related disorders.

Keywords: hypoxia; hypoxic pulmonary vasoconstriction; oxygen sensor; pulmonary hypertension; reactive oxygen species.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Electron Transport Complex IV / metabolism
  • Humans
  • Hypertension, Pulmonary / physiopathology*
  • Hypoxia / physiopathology*
  • Myocytes, Smooth Muscle / metabolism
  • Oxygen / metabolism*
  • Reactive Oxygen Species / metabolism
  • Signal Transduction*
  • Vasoconstriction*

Substances

  • Reactive Oxygen Species
  • Electron Transport Complex IV
  • Oxygen