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(Circulation Research. 2008;102:1451.)
© 2008 American Heart Association, Inc.

Editorials

Nitric Oxide–Mediated Zinc Release

A New (Modulatory) Pathway in Hypoxic Pulmonary Vasoconstriction

Norbert Weissmann

From the University of Giessen Lung Center, Medical Clinic II/V, Justus-Liebig-University Giessen, Germany.

Correspondence to Norbert Weissmann, University of Giessen Lung Center, Medical Clinic II/V, Justus-Liebig-University Giessen, Klinikstr. 36, D-35392 Giessen, Germany. E-mail Norbert.Weissmann@innere. med.uni-giessen.de

See related article, pages 1575–1583

Key Words: hypoxic pulmonary vasoconstriction • metallothionein • NO

An extract of the first 250 words of the full text is provided, because this article has no abstract.

	Introduction

 
Hypoxic pulmonary vasoconstriction (HPV) is an essential mechanism in the lung that redistributes pulmonary blood flow from areas of low oxygen tension to areas of high oxygen availability. This mechanism thus optimizes pulmonary gas exchange.^1–3 Impairment of HPV can result in severe hypoxemia. However, under conditions of global alveolar hypoxia, it becomes grossly ineffective and acute pulmonary hypertension occurs because of the overall contraction of the resistance vessels of the lung. Moreover, permanent activation of hypoxic vasoconstriction may contribute to the structural remodeling process of the pulmonary vasculature in chronic hypoxia.³

Despite the recognition of the importance of hypoxic vasoconstriction for pulmonary gas exchange by von Euler and Liljestrand in 1946, the underlying oxygen sensing and signal transduction processes have yet to be fully elucidated.⁴ Presently, mitochondria and NAD(P)H oxidases are proposed as possible oxygen sensors. However, there is great controversy as to the role of reactive oxygen species, ie, whether they are up- or downregulated in hypoxia, mediating HPV. The original redox hypothesis assumes a decrease in reactive oxygen species (ROS), shifting the cellular redox state toward a more reduced state and resulting in the inhibition of K_v channels in pulmonary arterial smooth muscle cells.² In contrast, there is also substantial evidence that an increase in ROS production during hypoxia triggers intracellular calcium release and thus the hypoxic vasoconstrictor response.^1,3

It is clearly evident that HPV is ultimately induced by an increase in intracellular calcium, and it is generally accepted that L-type calcium channels and K_v channels are essential . . . [Full Text of this Article]