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(Circulation. 2006;114:1531-1544.)
© 2006 American Heart Association, Inc.

Basic Science for Clinicians

Nitroso–Redox Interactions in the Cardiovascular System

Jeffrey M. Zimmet, MD; Joshua M. Hare, MD

From the Department of Medicine, Division of Cardiology, Institute for Cell Engineering, and Johns Hopkins University School of Medicine, Baltimore, Md.

Correspondence to Joshua M. Hare, MD, Johns Hopkins Medical Institutions and Institute for Cell Engineering, Division of Cardiology, BRB 651, 733 N Broadway, Baltimore, MD 21205. E-mail jhare@mail.jhmi.edu

Key Words: antioxidants • heart failure • nitric oxide • nitric oxide synthase • oxygen

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

	Introduction

 
Normal cardiovascular performance requires exquisite balancing of many complex biochemical processes. Perturbation of this balance may lead to myocardial dysfunction or may be a secondary result of structural heart disease such as myocardial infarction (MI) or cardiomyopathic processes. Altered signaling systems in turn contribute to the progression of myocardial dysfunction. The roles of reactive oxygen species (ROS) and reactive nitrogen species (RNS) in normal and failing myocardium and vasculature have been the subject of intense investigation and continue to engender considerable debate. A disturbance in the oxidation–reduction state of the cell, in which ROS production exceeds antioxidant defenses, is called oxidative stress. By analogy, nitrosative stress is an impairment in nitric oxide (NO) signaling caused by increased amounts of RNS, which may be caused by or associated with a disturbance in the redox state. This review addresses the role of the redox state and nitroso–redox balance in determining cardiovascular function in health and disease.

	The Chemistry of Nitroso–Redox Balance

 
Free radicals are highly reactive molecules with unpaired electrons. Free radical chemistry is the underpinning of 2 broad classes of signaling molecules in biological systems: ROS, which are reactive intermediates of oxygen metabolism, and a closely related group of RNS. The forms of ROS that are relevant in biological systems include the superoxide radical (O₂·^–), hydrogen peroxide (H₂O₂), and hydroxyl radical (OH·).¹ RNS of biological importance include NO, low- and high-molecular-weight S-nitrosothiols, and peroxynitrite (ONOO^–)² (Figure 1).

View larger version (16K): [in this window] [in a new window]   Figure 1. Sources of ROS and RNS. Superoxide is produced by a . . . [Full Text of this Article]

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