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J Am Coll Cardiol. 1998 Nov;32(5):1179-86.

Increased expression of constitutive nitric oxide synthase III, but not inducible nitric oxide synthase II, in human heart failure.

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1
Institüt für Experimentelle und Klinische Pharmakologie ünd Toxikologie, Abteilung Pharmakologie, Universitäts-Krankenhaus Eppendorf, Universität Hamburg, Germany.

Abstract

OBJECTIVES:

The purpose of the present study was to examine the expression of the endothelial-type nitric oxide synthase (NOS III) and the inducible-type NOS (NOS II) in human myocardium and their regulation in heart failure from patients with different etiologies.

BACKGROUND:

In heart failure, plasma levels of nitrates were found to be elevated. However, data on myocardial NOS expression in heart failure are conflicting.

METHODS:

Using RNase protection analysis and Western blotting, the expression of NOS III and NOS II was investigated in ventricular myocardium from nonfailing (NF) hearts (n=5) and from failing hearts of patients with idiopathic dilated cardiomyopathy (dCMP, n=14), ischemic cardiomyopathy (iCMP, n=9) or postmyocarditis cardiomyopathy (mCMP, n=7). Furthermore, immunohistochemical studies were performed to localize NOS III and NOS II within the ventricular myocardium.

RESULTS:

In failing human hearts, NOS III mRNA levels were increased to 180% in dCMP, 200% in iCMP and to 210% in mCMP as compared to NF hearts. Similarly, in Western blots (using constitutively expressed beta-tubulin as a reference) NOS III protein expression was increased about twofold in failing compared to NF hearts. Immunohistochemical studies with a selective antibody to NOS III showed no obvious differences in the staining of the endothelium of cardiac blood vessels from NF and failing human hearts. However, NOS III-immunoreactivity in cardiomyocytes was significantly more intense in failing compared to NF hearts. Low expression of NOS II mRNA was detected in only 2 of 30 failing human hearts and was not found in NF hearts. Inducible-type NOS protein was undetectable in either group.

CONCLUSIONS:

We conclude that the increased NOS III expression in the ventricular myocardium of failing human hearts may contribute to the contractile dysfunction observed in heart failure and/or may play a role in morphologic alterations such as hypertrophy and apoptosis of cardiomyocytes.

PMID:
9809923
DOI:
10.1016/s0735-1097(98)00399-4
[Indexed for MEDLINE]
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