(Circulation. 1999;100:635-641.)
© 1999 American Heart Association, Inc.
Clinical Investigation and Reports |
Preferential Impairment of Nitric Oxide–Mediated Endothelium-Dependent Relaxation in Human Cervical Arteries After Irradiation
From the Departments of Plastic and Reconstructive Surgery (T.S., Y.Y., F.Q.), Pharmacology (Y.H., A.S., M.-Y.L., M.K.), and Anatomy (R.I., K.A.), Hokkaido University School of Medicine, Sapporo, Japan.
Correspondence to Dr. Tsuneki Sugihara, Department of Plastic and Reconstructive Surgery, Hokkaido University School of Medicine, Sapporo 060-8638, Japan.
Background—Vascular abnormalities are a major cause of postoperative complications in irradiated tissues. Endothelial cell dysfunction characterized by diminished endothelium-dependent relaxation may be involved. We examined the endothelium-dependent relaxation and morphology of the endothelium in irradiated human cervical arteries.
Methods and Results—Irradiated arteries were taken from the neck
region of patients who had radiation therapy. Arteries from patients
who did not receive radiation therapy were used as controls.
Endothelium-dependent relaxation to acetylcholine and
A23187 was impaired in irradiated arteries.
Norepinephrine-induced contraction and sodium
nitroprusside–induced relaxation were unchanged. In control arteries,
N
-nitro-L-arginine and
indomethacin each caused a partial inhibition of
endothelium-dependent relaxation. In irradiated
arteries, the impaired endothelium-dependent relaxation
was unaffected by these agents, but it was abolished by high
K+. Acetylcholine produced similar degrees of
hyperpolarization in control and irradiated
arteries. Immunohistochemical examination for
endothelial nitric oxide synthase indicated no
expression in the endothelium of irradiated arteries.
Electron scanning microscopy showed morphologically intact
endothelial cells in irradiated arteries.
Conclusions—In irradiated human cervical arteries, the nitric oxide– and prostacyclin-mediated endothelium-dependent relaxation, but not endothelium-derived hyperpolarizing factor–mediated relaxation, are specifically impaired, without significant morphological damage of the endothelium. The impaired nitric oxide–mediated relaxation was associated with a lack of endothelial nitric oxide synthase expression. Our results suggest the importance of impaired endothelial function in irradiated human blood vessels, which may partly explain the development of vascular stenosis and poor surgical wound healing in irradiated tissues.
Key Words: arteries • endothelium • immunohistochemistry • vasodilation
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