Radiation therapy impairs endothelium-dependent vasodilation in humans

OBJECTIVES: The objective of this study was to test the hypothesis that external-beam radiation induces a chronic impairment of endothelium-dependent vasodilation. BACKGROUND: Radiation therapy is used commonly in the treatment of cancer and is associated with an increased incidence of adverse vascular events related to the field of radiation, including stroke and myocardial infarction. As endothelial injury is central to the pathogenesis of vascular diseases, we hypothesized that radiotherapy induces arterial endothelial dysfunction. METHODS: Sixteen women with unilateral breast cancer who underwent standard external-beam radiation therapy to the breast and axilla >3 years before enrollment and ten healthy women were studied. Vascular ultrasonography was used to image both the artery exposed to radiation and the contralateral artery. Flow-mediated, endothelium-dependent vasodilation and endothelium-independent vasodilation to nitroglycerin of both axillary arteries were measured. RESULTS: Endothelium-dependent vasodilation was significantly impaired in the irradiated axillary arteries compared with the contralateral, nonirradiated arteries (-0.4 ± 0.4% vs. 3.2 ± 0.8%, p < 0.001) and also compared with control subjects' arteries (-0.4 ± 0.4% vs. 2.5 ± 0.6%, p < 0.001). In contrast, endothelium-independent vasodilation was greater in the arteries that received radiation compared with the contralateral arteries (3.8 ± 0.5% vs. 2.0 ± 0.4%, p < 0.05) and also compared with control arteries (3.8 ± 0.5% vs. 2.5 ± 0.4%, p < 0.05). CONCLUSIONS: External beam radiation therapy impairs endothelium-dependent vasodilation of conduit arteries, implicating a decrease in the bioavailability of nitric oxide. These abnormalities may contribute to the development of arterial occlusive disease and associated clinical events.