Mechanisms of selective impairment of nitric oxide-mediated endothelium-dependent vasodilation following ionizing irradiation

A. Soloviev, S. Tishkin, A. Gurney

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    The endothelium is the main target in the vascular wall for ionizing radiation; an irradiation-induced impairment leads to the loss of endothelium-dependent vasodilation. Recent studies showed that gamma irradiation causes selective impairment of nitric oxide (NO)-mediated vasodilation, but little is known about the underlying mechanisms. The goal of our study was to identify mechanisms underlying the impairment of NO-mediated endothelium-dependent vasodilation after whole-body irradiation with a cobalt60 source. We compared vasodilation and NO release induced by acetylcholine (ACh), as well as relaxations induced by exogenous NO, in the thoracic aorta from healthy and irradiated rabbits. It was shown that despite the loss of relaxation the apparent release of NO induced by ACh and detected by chemiluminescence assay remained unaltered in irradiated tissue, as compared with that of healthy rabbits. At the same time, it was evident that while in healthy vessels relaxation increased with increasing NO concentration, this relationship was lost in irradiated vessels. Endothelium-denuded aortic smooth muscles from irradiated rabbits retained the same sensitivity to NO gas solution as healthy denuded vessels. When non-denuded vascular tissues were used, irradiated aortas demonstrated an increased sensitivity, as compared with non-irradiated vascular tissue. α-Tocopherol acetate and phosphatidylcholine liposomes, when administered to rabbits 1 h after irradiation, effectively restored the NO-mediated endothelium-dependent relaxation and normalized the relationship between NO release and relaxation and also the sensitivity of the vessels to inhibition by Nω-nitro-L-arginine (L-NA). Taken together, these data allow us to hypothesize that inhibition of an EDRF/NO-dependent component of vascular relaxation in irradiated rabbits may be due to at least two possible reasons: (i) intensified inactivation of endothelium-derived NO by oxygen free radicals, and (ii) abnormalities in diffusion of NO in the irradiated endothelium and subendothelial layer. Both these effects may lead to a decrease in the bioavailability of NO.
    Original languageEnglish
    Pages (from-to)248-255
    Number of pages7
    Issue number3-4
    Publication statusPublished - May 2003


    • α-Tocopherol
    • Endothelium
    • No bioavailability
    • Phosphatidycholine liposomes
    • Radiation


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