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


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(omega)-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.
Sugihara
T
T
Department of Plastic and Reconstructive Surgery, Hokkaido University School of Medicine, Sapporo, Japan.
Hattori
Y
Y
Yamamoto
Y
Y
Qi
F
F
Ichikawa
R
R
Sato
A
A
Liu
M Y
MY
Abe
K
K
Kanno
M
M
D000109:Acetylcholine / Q000494:pharmacology; D000328:Adult; D000368:Aged; D001158:Arteries / Q000293:injuries / Q000528:radiation effects; D000001:Calcimycin / Q000494:pharmacology; D003131:Combined Modality Therapy; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000293:injuries / Q000503:physiopathology / Q000528:radiation effects*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006258:Head and Neck Neoplasms / Q000532:radiotherapy / Q000601:surgery; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D008875:Middle Aged; D009126:Muscle Relaxation / Q000187:drug effects / Q000528:radiation effects; D009131:Muscle, Smooth, Vascular / Q000293:injuries / Q000503:physiopathology*; D009333:Neck / Q000098:blood supply*; D037981:Neck Dissection; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000032:analysis / Q000037:antagonists & inhibitors; D052250:Nitric Oxide Synthase Type III; D019335:Nitroarginine / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D011832:Radiation Injuries / Q000503:physiopathology*; D011878:Radiotherapy / Q000009:adverse effects*; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects / Q000528:radiation effects*; D014665:Vasodilator Agents / Q000494:pharmacology
D016861:Cyclooxygenase Inhibitors; D004791:Enzyme Inhibitors; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D009599:Nitroprusside; D019335:Nitroarginine; D009569:Nitric Oxide; D000001:Calcimycin; C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; D000109:Acetylcholine; D011188:Potassium; D009638:Norepinephrine; D007213:Indomethacin