Nitric oxide and nitric oxide synthase isoforms in the normal, hypertrophic, and failing heart

Article

Abstract

Nitric oxide (NO) produced in the heart by nitric oxide synthase (NOS) is a highly reactive signaling molecule and an important modulator of myocardial function. NOS catalyzes the conversion of l-arginine to l-citrulline and NO but under particular circumstances reactive oxygen species (ROS) can be formed instead of NO (uncoupling). In the heart, three NOS isoforms are present: neuronal NOS (nNOS, NOS1) and endothelial NOS (eNOS, NOS3) are constitutively present enzymes in distinct subcellular locations within cardiomyocytes, whereas inducible NOS (iNOS, NOS2) is absent in the healthy heart, but its expression is induced by pro-inflammatory mediators. In the tissue, NO has two main effects: (i) NO stimulates the activity of guanylate cyclase, leading to cGMP generation and activation of protein kinase G, and (ii) NO nitrosylates tyrosine and thiol-groups of cysteine in proteins. Upon nitrosylation, proteins may change their properties. Changes in (i) NOS expression and activity, (ii) subcellular compartmentation of NOS activity, and (iii) the occurrence of uncoupling may lead to multiple NO-induced effects, some of which being particularly evident during myocardial overload as occurs during aortic constriction and myocardial infarction. Many of these NO-induced effects are considered to be cardioprotective but particularly if NOS becomes uncoupled, formation of ROS in combination with a low NO bioavailability predisposes for cardiac damage.

Keywords

Nitric oxide Hypertrophy Nitric oxide synthase Heart failure 

Abbreviations

NO

Nitric oxide

nNOS

Neuronal nitric oxide synthase

eNOS

Endothelial nitric oxide synthase

iNOS

Inducible nitric oxide synthase

IFN

Interferon

LPA

Lipopolysaccharide

cGMP

Cyclic guanosine monophosphate

GTP

Guanosine triphosphate

PKG

Protein kinase G

LV

Left ventricle

RGD

Arg-gly-asp motif (in peptide)

IL6

Interleukin 6

TNFα

Tumor necrosis factor alpha

l-NAME

Nω-nitro-l-arginine methyl ester

ACE

Angiotensin converting enzyme

ROS

Reactive oxygen species

RyR

Ryanodine receptor

SR

Sarcoplasmic reticulum

MMP

Matrix metalloproteinase

IL-1β

Interleukin-1 beta

SERCA

Sarcoplasmic reticulum calcium ATPase

PO

Probability of a channel to be open

RV

Right ventricle

NADPH

Nicotinamide adenine dinucleotide phosphate

CHF

Congestive heart failure

l-NMMA

NG-monomethyl-l-arginine

XOD

Xanthine oxidoreductase

BH4

Tetrahydrobiopterin

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Copyright information

© Springer Science+Business Media, LLC. 2009

Authors and Affiliations

  1. 1.Department of CardiologyLeiden University Medical CenterLeidenThe Netherlands

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