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Eur Respir J 2008; 32:1639-1651
Copyright ©ERS Journals Ltd 2008

Regulation of hypoxic pulmonary vasoconstriction: basic mechanisms

N. Sommer1, A. Dietrich2, R. T. Schermuly1, H. A. Ghofrani1, T. Gudermann2, R. Schulz1, W. Seeger1, F. Grimminger1 and N. Weissmann1

1 University of Giessen Lung Center, Medical Clinic II/V, Justus-Liebig-University Giessen, Giessen, and 2 Philipps-University Marburg, Institute of Pharmacology and Toxicology, Marburg, Germany.

CORRESPONDENCE: N. Weissmann, University of Giessen Lung Center, Medical Clinic II/V, Justus-Liebig-University Giessen, 35392 Giessen, Germany. Fax: 49 6419942419. E-mail: norbert.weissmann{at}uglc.de

Keywords: Hypoxia, hypoxic pulmonary vasoconstriction, lung, oxygen, oxygen sensing

Received: January 29, 2008
Accepted May 2, 2008

Hypoxic pulmonary vasoconstriction (HPV), also known as the von Euler–Liljestrand mechanism, is a physiological response to alveolar hypoxia which distributes pulmonary capillary blood flow to alveolar areas of high oxygen partial pressure.

Impairment of this mechanism may result in hypoxaemia. Under conditions of chronic hypoxia generalised vasoconstriction of the pulmonary vasculature in concert with hypoxia-induced vascular remodelling leads to pulmonary hypertension. Although the principle of HPV was recognised decades ago, its exact pathway still remains elusive. Neither the oxygen sensing process nor the exact pathway underlying HPV is fully deciphered yet. The effector pathway is suggested to include L-type calcium channels, nonspecific cation channels and voltage-dependent potassium channels, whereas mitochondria and nicotinamide adenine dinucleotide phosphate oxidases are discussed as oxygen sensors. Reactive oxygen species, redox couples and adenosine monophosphate-activated kinases are under investigation as mediators of hypoxic pulmonary vasoconstriction. Moreover, the role of calcium sensitisation, intracellular calcium stores and direction of change of reactive oxygen species is still under debate.

In this context the present article focuses on the basic mechanisms of hypoxic pulmonary vasoconstriction and also outlines differences in current concepts that have been suggested for the regulation of hypoxic pulmonary vasoconstriction.




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