Preferential impairment of nitric oxide-mediated endothelium-dependent relaxation in human cervical arteries after irradiation

Background-Vascular abnormalities are a major cause of postoperative compli cations in irradiated tissues. Endothelial cell dysfunction characterized b y diminished endothelium-dependent relaxation may be involved. We examined the endothelium-dependent relaxation and morphology of the endothelium in i rradiated 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 rece ive radiation therapy were used as controls. Endothelium-dependent relaxati on to acetylcholine and A23187 was impaired in irradiated arteries. Norepin ephrine-induced contraction and sodium nitroprusside-induced relaxation wer e unchanged. In control arteries, N-omega-nitro-L-arginine and indomethacin each caused a partial inhibition of endothelium-dependent relaxation. In i rradiated arteries, the impaired endothelium-dependent relaxation was unaff ected by these agents, but it was abolished by high K+. acetylcholine produ ced similar degrees of hyperpolarization in control and irradiated arteries . Immunohistochemical examination for endothelial nitric oxide synthase ind icated no expression in the endothelium of irradiated arteries. Electron sc anning microscopy showed morphologically intact endothelial cells in irradi ated arteries. Conclusions-In irradiated human cervical arteries, the nitric oxide- and pr ostacyclin-mediated endothelium-dependent relaxation, but not endothelium-d erived hyperpolarizing factor-mediated relaxation, are specifically impaire d, without significant morphological damage of the endothelium. The impaire d nitric oxide-mediated relaxation was associated with a lack of endothelia l nitric oxide synthase expression. Our results suggest the importance of i mpaired endothelial function in irradiated human blood vessels, which may p artly explain the development of vascular stenosis and poor surgical wound healing in irradiated tissues.