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(Circulation Research. 2008;102:148.)
© 2008 American Heart Association, Inc.

Editorials

Neuronal NO Synthase–Derived NO

A Novel Relaxing Factor in Myocardium?

Norio Fukuda, Jin O-Uchi, Satoshi Kurihara

From the Department of Cell Physiology, The Jikei University School of Medicine, Tokyo, Japan.

Correspondence to Norio Fukuda or Satoshi Kurihara, Department of Cell Physiology, The Jikei University School of Medicine, 3-25-8 Nishi-shinbashi, Minato-ku, Tokyo 105-8461, Japan. E-mail noriof@jikei.ac.jp or kurihara@jikei.ac.jp

See related article, pages 242–249

Key Words: myocardium • nNOS • relaxation • sarcoplasmic reticulum • phosphorylation

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

Nitric oxide (NO) is generated by a family of NO synthases (NOSs) and is involved in a number of physiological and pathological processes in the cardiovascular system, most notably in the vasculature.¹ The classic and, therefore, best-established action is its paracrine action in blood vessels, maintaining homeostasis, in that NO released from the endothelium reduces the tone of the vascular smooth muscle cells via activation of cGMP-dependent protein kinase (PKG).² In the heart, 2 distinct types of NOSs, known as endothelial NOS (eNOS) and neuronal NOS (nNOS), are expressed in physiological settings (see elsewhere^3,4 and references therein). Although both eNOS and nNOS are expressed in cardiomyocytes, they are localized to distinct subcellular compartments; that is, eNOS is localized to caveolae in the sarcolemma,⁵ whereas nNOS is localized predominantly to the sarcoplasmic reticulum (SR).⁶

In this issue of Circulation Research, Casadei and colleagues have refined our understanding of the role of nNOS-derived NO in the regulation of cardiac contractility, providing evidence that nNOS-derived NO accelerates ventricular relaxation via a cGMP/PKG-independent mechanism.⁷ Before discussing their novel findings, we would like to briefly summarize the mechanisms of cardiac muscle relaxation (Figure 1), based on the literature.⁸

View larger version (13K):   Figure 1. Summary of players in myocardial relaxation. [Ca2+]i- and myofilament-based controls are documented. (The Ca2+ removal process via mitochondria is not shown for simplicity.) Proteins that are phosphorylated by PKA are marked in red. See the text for details.

On stimulation of cardiomyocytes, Ca²⁺ enters the myocyte via sarcolemmal L-type Ca²⁺ . . . [Full Text of this Article]

Related Article:

Reduced Phospholamban Phosphorylation Is Associated With Impaired Relaxation in Left Ventricular Myocytes From Neuronal NO Synthase–Deficient Mice

Yin Hua Zhang, Mei Hua Zhang, Claire E. Sears, Krzysztof Emanuel, Charles Redwood, Ali El-Armouche, Evangelia G. Kranias, and Barbara Casadei
Circ. Res. 2008 102: 242-249. [Abstract] [Full Text] [PDF]