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(Circulation Research. 2002;91:649.)
© 2002 American Heart Association, Inc.

Editorials

Hypoxic Pulmonary Vasoconstriction

Ups and Downs of Reactive Oxygen Species

James S.K. Sham

From the Division of Pulmonary and Critical Care Medicine, Johns Hopkins Medical Institutions, Baltimore, Md.

Correspondence to James S.K. Sham, Division of Pulmonary and Critical Care Medicine, Johns Hopkins Medical Institutions, Baltimore, MD 21224. E-mail jsks@welchlink.welch.jhu.edu

Key Words: hydrogen peroxide • calcium • ryanodine receptor • hypoxia

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

Reduction in alveolar oxygen tension causes reversible hypoxic pulmonary vasoconstriction (HPV), which is thought to serve as an adaptive mechanism for diverting blood flow from poorly ventilated to better-ventilated regions of the lung to improve ventilation-perfusion matching. Since first described by Von Euler and Liljestrand¹ 50 years ago, significant advances have been made in determining the O₂ dependence, temporal characteristics, loci of response, physiological conditions, and neurohumoral factors that influence HPV in intact animal, isolated lung, and pulmonary arterial rings. Recent studies using isolated pulmonary arterial smooth muscle cells (PASMCs) indicate that hypoxia directly causes membrane depolarization, increase in intracellular [Ca²⁺], and cell-shortening; thus, the essential elements of HPV are contained in PASMCs, even though one or more endothelially derived mediators, such as ET-1 and/or an unknown factor,^2,3 are required for the full expression of hypoxic response. However, despite this progress, the precise cellular mechanism of O₂ sensing for HPV remains controversial.

There are several proposed mechanisms for O₂ sensing in PASMCs, most of which are related to reactive oxygen species (ROS).⁴ The first hypothesis proposed that a smooth muscle microsomal NADH oxidoreductase, which generates H₂O₂ via a PO₂-dependent production of superoxide, acts as the O₂ sensor; H₂O₂ interacts with catalase to activate soluble guanylate cyclase and increase cGMP to provide tonic vasorelaxation during normoxia.^5,6 Under hypoxic conditions, production of H₂O₂ from NADH oxidase would be reduced, leading to the removal of the vasorelaxant influence, and pulmonary vasoconstriction.

The second hypothesis proposed that hypoxia . . . [Full Text of this Article]

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