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(Circulation Research. 2007;101:224.)
© 2007 American Heart Association, Inc.

Editorials

The NOX on Pulmonary Hypertension

Karl A. Sanders, John R. Hoidal

From the Division of Respiratory, Critical Care and Occupational Pulmonary Medicine (K.A.S., J.R.H.), University of Utah Health Sciences Center and Veterans Affairs Medical Center, Salt Lake City.

Correspondence to John R. Hoidal, Department of Medicine. University of Utah Medical Center, 26 North 1900 East, Salt Lake City, UT 84132. E-mail John.Hoidal@hsc.utah.edu

See related article, pages 258–267

Key Words: NOX4 • NADPH oxidase • hypoxia • pulmonary hypertension

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

Chronic pulmonary arterial hypertension (PAH) is a devastating clinical disorder that contributes to the morbidity and mortality of adult and pediatric patients with a wide range of lung and heart diseases. Diseases leading to pulmonary hypertension are frequently associated with hypoxia within discrete areas of the lung. Acutely, the regional response to hypoxia is a reversible contraction of pulmonary artery smooth muscle cells (PASMC), which is a protective physiologic response that serves to redirect blood to better-ventilated areas of the lung. This constrictor response of PASMC contrasts with that of systemic arterial smooth muscle cells, which usually relax in response to hypoxia, indicating that oxygen (O₂) sensing mechanisms in vascular smooth muscle are adapted to the environment from which they are derived. Importantly, chronic hypoxia induces irreversible changes of profound vascular remodeling characterized by medial and adventitial thickening of the muscular and elastic vessels and muscularization of previously nonmuscularized more distal small vessels. This is the basis for debilitating persistent PAH.¹

Reactive oxygen species (ROS) are important regulators of vascular tone and function.^2,3 In the lung, ROS are implicated in acute hypoxic vasoconstriction.⁴ Administration of superoxide dismutase significantly attenuates pulmonary vasoconstriction because of hypoxia.⁵ Moreover, several studies have now shown that agents promoting ROS generation stimulate both systemic arterial smooth muscle cells and PASMC proliferation implicating ROS in the vascular remodeling associated with chronic hypoxia. Again, suppression of endogenous ROS production inhibits smooth muscle cell (SMC) proliferation and promotes apoptosis.^6–8 In animal models, ROS production has been directly linked . . . [Full Text of this Article]

Related Article:

Hypoxia-Dependent Regulation of Nonphagocytic NADPH Oxidase Subunit NOX4 in the Pulmonary Vasculature

Manish Mittal, Markus Roth, Peter König, Simone Hofmann, Eva Dony, Parag Goyal, Anne-Christin Selbitz, Ralph Theo Schermuly, Hossein Ardeschir Ghofrani, Grazyna Kwapiszewska, Wolfgang Kummer, Walter Klepetko, Mir Ali Reza Hoda, Ludger Fink, Jörg Hänze, Werner Seeger, Friedrich Grimminger, Harald H.H.W. Schmidt, and Norbert Weissmann
Circ. Res. 2007 101: 258-267. [Abstract] [Full Text] [PDF]

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