Involvement of inducible nitric oxide synthase in radiation-Induced vascular endothelial damage

Chang Won Hong, Young-Mee Kim, Hongryull Pyo, Joon Ho Lee, Suwan Kim, Sunyoung Lee, Jae Myoung Noh

Research output: Contribution to journalArticle

16 Scopus citations

Abstract

The use of radiation therapy has been linked to an increased risk of cardiovascular disease. To understand the mechanisms underlying radiation-induced vascular dysfunction, we employed two models. First, we examined the effect of X-ray irradiation on vasodilation in rabbit carotid arteries. Carotid arterial rings were irradiated with 8 or 16 Gy using in vivo and ex vivo methods. We measured the effect of acetylcholine-induced relaxation after phenylephrine-induced contraction on the rings. In irradiated carotid arteries, vasodilation was significantly attenuated by both irradiation methods. The relaxation response was completely blocked by 1H-[1,2,4]oxadiazolo[4,3- a]quinoxalin-1-one, a potent inhibitor of soluble guanylate cyclase. Residual relaxation persisted after treatment with L-Nω-nitroarginine (L-NA), a non-specific inhibitor of nitric oxide synthase (NOS), but disappeared following the addition of aminoguanidine (AG), a selective inhibitor of inducible NOS (iNOS). The relaxation response was also affected by tetraethylammonium, an inhibitor of endothelium-derived hyperpolarizing factor activity. In the second model, we investigated the biochemical events of nitrosative stress in human umbilical-vein endothelial cells (HUVECs). We measured iNOS and nitrotyrosine expression in HUVECs exposed to a dose of 4 Gy. The expression of iNOS and nitrotyrosine was greater in irradiated HUVECs than in untreated controls. Pretreatment with AG, L-N6-(1-iminoethyl) lysine hydrochloride (a selective inhibitor of iNOS), and L-NA attenuated nitrosative stress. While a selective target of radiation-induced vascular endothelial damage was not definitely determined, these results suggest that NO generated from iNOS could contribute to vasorelaxation. These studies highlight a potential role of iNOS inhibitors in ameliorating radiation-induced vascular endothelial damage.

Original languageEnglish (US)
Pages (from-to)1036-1042
Number of pages7
JournalJournal of radiation research
Volume54
Issue number6
DOIs
StatePublished - Nov 1 2013

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Keywords

  • Inducible nitric oxide synthase
  • Nitrotyrosine
  • Radiation injuries
  • Vascular endothelium

ASJC Scopus subject areas

  • Radiation
  • Radiology Nuclear Medicine and imaging
  • Health, Toxicology and Mutagenesis

Cite this

Hong, C. W., Kim, Y-M., Pyo, H., Lee, J. H., Kim, S., Lee, S., & Noh, J. M. (2013). Involvement of inducible nitric oxide synthase in radiation-Induced vascular endothelial damage. Journal of radiation research, 54(6), 1036-1042. https://doi.org/10.1093/jrr/rrt066