(Circulation. 1999;99:2972-2975.)
© 1999 American Heart Association, Inc.
Editorial |
Nitric Oxide Synthases in the Failing Human Heart
A Doubled-Edged Sword?
From the Abteilung Kardiologie, Medizinische Hochschule Hannover, Hannover, Germany.
Correspondence to Helmut Drexler, MD, Carl-Neubergstr.1, 30625 Hannover, Germany. E-mail Drexler.Helmut@MH-Hannover.de
Key Words: Editorials • nitric oxide • heart failure • nitric oxide synthase • apoptosis
Nitric oxide (NO) is a free radical gas and is readily diffusible; it has a very short half-life, lasting only seconds. NO is synthesized from L-arginine by the catalytic reaction of different isoforms of nitric oxide synthases, including the neuronal, type 1 isoform (nNOS [NOS1]); the inducible, type 2 isoform (iNOS [NOS2]); and the endothelial, type 3 isoform (eNOS [NOS3]). nNOS and eNOS are constitutively expressed enzymes and are regulated predominantly at the posttranslational level, whereas in most cell types, iNOS can be essentially expressed in response to appropriate stimuli.1 Small amounts of NO, produced by nNOS and eNOS, are involved in signal events that regulate neurotransmission and vascular tone. Because the activity of nNOS and eNOS is triggered, it is transient. Much larger concentrations of NO are usually provided by iNOS in cells during infection and inflammation; however, because iNOS is independent of stimulating agonists and Ca2+, its activity is sustained.1
Both nNOS and eNOS are constitutively expressed in the
myocardium; nNOS is expressed in nerve endings involved in
the neurotransmission of norepinephrine,2 and
eNOS is expressed in endothelial cells,3
endocardial cells, and cardiomyocytes.4 In
disease states associated with infection, inflammation, or
cytokine activation, the expression of iNOS is clearly
demonstrated in the heart, including in the
cardiomyocytes.4 The ubiquitous distribution
of NO synthases within the myocardium and the versatile
actions of NO make this molecule unique in the diverse cardiac effects
that depend on its concentration and the spatial and temporal activity
of its isoforms. The
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