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

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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.

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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

P O :

Probability of a channel to be open

RV:

Right ventricle

NADPH:

Nicotinamide adenine dinucleotide phosphate

CHF:

Congestive heart failure

l-NMMA:

N G-monomethyl-l-arginine

XOD:

Xanthine oxidoreductase

BH4 :

Tetrahydrobiopterin

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  1. Department of Cardiology, Leiden University Medical Center, P.O. Box 9600, 2300 RC, Leiden, The Netherlands

    Soban Umar & Arnoud van der Laarse

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Umar, S., van der Laarse, A. Nitric oxide and nitric oxide synthase isoforms in the normal, hypertrophic, and failing heart. Mol Cell Biochem 333, 191–201 (2010). https://doi.org/10.1007/s11010-009-0219-x

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