Hypoxic Pulmonary Vasoconstriction - Invited Article

A. M. Evans, J. P. T. Ward

Research output: Chapter in Book/Report/Conference proceedingConference contribution

Abstract

Hypoxic pulmonary vasoconstriction (HPV) is an adaptive mechanism that in the face of localised alveolar hypoxia diverts blood away from poorly ventilated regions of the lung, thereby preserving ventilation/perfusion matching. HPV has been recognised for many years, but although the underlying mechanisms are known to reside within the arteries themselves, their precise nature remains unclear. There is a growing consensus that mitochondria act as the oxygen sensor, and that Ca2+ release from ryanodine-sensitive stores and Rho kinase-mediated Ca2+ sensitisation are critical for sustained vasoconstriction, though Ca2+ entry via both voltage-dependent and/or -independent pathways has also been implicated. There is, however, controversy regarding the signalling pathways that link the oxygen sensor to its effectors, with three main hypotheses. The AMP-activated protein kinase (AMPK) hypothesis proposes that hypoxic inhibition of mitochondrial function increases the AMP/ATP ratio and thus activates AMPK, which in turn mediates cADPR-dependent mobilisation of ryanodine-sensitive sarcoplasmic reticulum Ca2+ stores. In contrast the two other hypotheses invoke redox signalling, albeit in mutually incompatible ways. The Redox hypothesis proposes that hypoxia suppresses mitochondrial generation of reactive oxygen species (ROS) and causes the cytosol to become more reduced, with subsequent inhibition of K-V channels, depolarisation and voltage-dependent Ca2+ entry. In direct contrast the ROS hypothesis proposes that hypoxia causes an apparently paradoxical increase in mitochondrial ROS generation, and it is this increase in ROS that acts as the signalling moiety. In this article we describe our current understanding of HPV, and evidence in support of these models of oxygen-sensing.

Original languageEnglish
Title of host publicationArterial Chemoreceptors
EditorsConstancio Gonzalez, A. Colin Nurse, Chris Peers
Place of PublicationBERLIN
PublisherSpringer-Verlag GmbH
Pages351-360
Number of pages10
Volume648
ISBN (Print)978-90-481-2258-5
DOIs
Publication statusPublished - 2009
Event17th Meeting of the International-Society-for-Arterial-Chemoreception (ISAC) - Valladolid
Duration: 1 Jul 20085 Jul 2008

Conference

Conference17th Meeting of the International-Society-for-Arterial-Chemoreception (ISAC)
CityValladolid
Period1/07/085/07/08

Keywords

  • Hypoxic pulmonary vasoconstriction
  • Alveolar hypoxia
  • Ventilation
  • Mitochondria
  • Oxygen-sensor
  • Calcium
  • AMP-activated protein kinase
  • AMPK
  • Sarcoplasmic reticulum Kv chennel

Fingerprint Dive into the research topics of 'Hypoxic Pulmonary Vasoconstriction - Invited Article'. Together they form a unique fingerprint.

Cite this