From Cardiovascular Research, Institute of Physiology, University of
Zürich (B.S.O., M.R.T.); Cardiology, University Hospital Zürich
(T.F.L.); and Neurosurgery, University Hospital Bern (N.G.), Switzerland; and
the Department of Chemistry, Institute of Biotechnology, Oakland University,
Rochester, Minn (V.B., T.M.).
Correspondence to Thomas F. Lüscher, MD, Professor and Head of Cardiology, University Hospital Zürich, CH-8091 Zürich, Switzerland. E-mail karluh{at}usz.unizh.ch
Background—NO regulates vascular
tone and structure, platelets, and monocytes. NO is synthesized by
endothelial NO synthase (eNOS).
Endothelial dysfunction occurs in
atherosclerosis.
Methods and Results—With a porphyrinic microsensor, NO release
was measured in atherosclerotic human carotid arteries and normal
mammary arteries obtained during surgery. eNOS protein expression was
analyzed by immunohistochemistry. In normal arteries, the
initial rate of NO release after stimulation with calcium ionophore
A23187 (10 µmol/L) was 0.42±0.05 (µmol/L)/s (n=10). In
contrast, the initial rate of NO release was markedly reduced in
atherosclerotic segments, to 0.08±0.04 (µmol/L)/s (n=10,
P<0.0001). NO peak concentration in normal arteries was
0.9±0.09 µmol/L (n=10) and in atherosclerotic segments,
0.1±0.03 µmol/L (n=10, P<0.0001). Reduced NO
release in atherosclerotic segments was accompanied by marked reduction
of immunoreactive eNOS in luminal endothelial cells,
although specific endothelial cell markers (CD31) were
present (n=13). Endothelial cells of vasa vasorum
of atherosclerotic segments, however, remained positive for eNOS, as
was the endothelium of normal arteries.
Conclusions—In clinically relevant human
atherosclerosis, eNOS protein expression and NO release
are markedly reduced. This may be involved in the progression of
atherosclerosis.
© 1998 American Heart Association, Inc.
Brief Rapid Communications
Reduced Endothelial Nitric Oxide Synthase Expression and Production in Human Atherosclerosis
Key Words: atherosclerosis • arteries • endothelium • nitric oxide • stroke
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