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(Circulation. 2005;112:3668-3671.)
© 2005 American Heart Association, Inc.

Editorial

"La Donna è Mobile..."

Is Cardiac Neuronal Nitric Oxide Synthase Such a Disconcerting Enzyme?

J.-L. Balligand, MD, PhD

From the Unit of Pharmacology and Therapeutics (FATH 5349), Department of Medicine, Université catholique de Louvain, Brussels, Belgium.

Correspondence to J.-L. Balligand, MD, PhD, Unit of Pharmacology and Therapeutics (FATH 5349), Department of Medicine, Université catholique de Louvain, 53 Avenue Mounier, 1200 Brussels, Belgium. E-mail Balligand@mint.ucl.ac.be

Key Words: Editorials • contractility • myocardial infarction • nitric oxide synthase • remodeling

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

	Introduction

 
As a prototypical vasorelaxant, nitric oxide (NO) produced by the endothelium indirectly regulates cardiac function through its modulation of the coronary reserve and peripheral hemodynamics. Since the initial description of a direct, autocrine regulation of cardiomyocyte contraction by a constitutive nitric oxide synthase,¹ a substantial body of evidence has confirmed the pleiotropic effects of NO produced within cardiac myocytes on many aspects of their cellular biology, such as oxygen consumption,² excitation-contraction (EC) coupling,³ and hypertrophic remodeling⁴ (for a review, see elsewhere⁵).

Article p 3729

	Which and Where Are the Cardiac Nitric Oxide Synthases?

 
The endothelial nitric oxide synthase (eNOS; encoded by the NOS3 gene) and the neuronal nitric oxide synthase (nNOS; encoded by NOS1) are the 2 constitutive NOSs expressed in cardiac myocytes. eNOS is enriched in plasmalemmal and T-tubular caveolae,⁶ where it colocalizes with caveolin-3 (the myocyte-specific structural protein of caveolae). One study⁷ identified nNOS in sarcoplasmic reticulum (SR) membranes of normal rabbit and human hearts; there is also biochemical evidence for nNOS expression in mitochondria.⁸ In addition, nNOS is abundantly expressed in cardiac adrenergic and cholinergic nervous fibers, and eNOS is expressed in both endothelial and endocardial cells. On ischemia or sepsis, inflammatory cytokines induce the expression of the calcium-independent NOS (inducible nitric oxide synthase [iNOS], encoded by NOS2) in cardiomyocytes and inflammatory cells infiltrating the myocardium.

At first glance, this multiplicity of NOS isoforms would hardly be compatible with signaling specificity on limited (sub)cellular targets a fortiori given the theoretical diffusibility of NO as a gas. In muscle cells, however, the abundant distribution . . . [Full Text of this Article]

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