From the Departments of Medicine and Pathology, The Montreal General
Hospital and McGill University, and GenPath Laboratories, Montreal, Quebec,
Canada H3G 1A4.
Correspondence to Dr Adel Giaid, Suite L3–314, The Montreal General Hospital, 1650 Cedar Ave, Montreal, Quebec, Canada H3G 1A4. E-mail mdga{at}musica.mcgill.ca
Background—Recent reports have
suggested that excessive amounts of endogenous NO may
contribute to the myocardial dysfunction and injury in heart failure.
In the present report, we investigate the cellular expression and
activity of endothelial (eNOS) and inducible (iNOS) NO
synthase in failing human hearts with special reference to the
underlying lesion and drug therapy.
Methods and Results—Myocardial tissues were obtained from 28
failing human hearts with various pathogeneses and 4 nonfailing hearts
as controls. Only weak or focal expression of both eNOS and iNOS was
seen in ventricles of nonfailing hearts. In failing hearts,
immunoreactivity and hybridization signals for eNOS were increased only
in cardiac myocytes of subendocardial areas. Signals for iNOS in
cardiac myocytes were consistently seen in heart failure of
various pathogeneses and were apparent in both infarcted and
noninfarcted regions of ischemic
cardiomyopathy. Apparent signals for iNOS were also
seen in infiltrating macrophages in infarcted regions of
ischemic cardiomyopathy, myocarditis, and
septic hearts. The expression of eNOS but not iNOS in the myocytes was
intimately associated with ß-adrenergic therapy before the operation,
being more abundant in patients on ß-blockers compared with
diminished presence in patients on ß-agonists. In contrast to
immunohistochemical data, iNOS activity was more variable than
constitutive NOS activity and correlated significantly with the density
of infiltrating macrophages.
Conclusions—These results suggest that whereas increased eNOS
and/or iNOS expression in failing cardiac myocytes may in general
contribute to myocardial dysfunction, myocyte injury or death
associated with inflammatory lesions may be caused in part by abundant
iNOS expression within infiltrating macrophages rather than
cardiac myocytes.
© 1998 American Heart Association, Inc.
Clinical Investigation and Reports
Heterogeneous Expression and Activity of Endothelial and Inducible Nitric Oxide Synthases in End-Stage Human Heart Failure
Their Relation to Lesion Site and ß-Adrenergic Receptor Therapy
Key Words: cells • biopsy • RNA • immunohistochemistry
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