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Radiation impairs endothelium‐dependent dilation of murine intestinal arterioles via reduction of nitric oxide by reactive oxygen species
Author(s) -
Larsen Brandon T,
Otterson Mary F,
Miura Hiroto,
Phillips Shane A,
Selle Rebecca M,
Gutterman David D,
Hatoum Ossama A
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.a1162
Subject(s) - nitric oxide , dilator , reactive oxygen species , vasodilation , endothelium , chemistry , superoxide dismutase , acetylcholine , constriction , endocrinology , medicine , oxidative stress , pharmacology , biochemistry
Vascular dysregulation may contribute to radiation toxicity. Although radiation impairs acetylcholine (Ach)‐induced vasodilation and induces production of reactive oxygen species (ROS) in the gut, its effect on nitric oxide (NO) bioavailability is unclear. Rats were irradiated with 2250 cGy over 3 weeks. Isolated intestinal submucosal arterioles were cannulated, pressurized, and diameter changes were measured by videomicroscopy. Following constriction (30–50%) with endothelin‐1, Ach‐induced dilation was minimal in irradiated vessels, but was partially restored when tempol (10 −4 M, a superoxide dismutase [SOD] mimetic) was present in the drinking water during irradiation (9 ± 4% vs. 44 ± 6% at 10 −4 M, respectively; n = 5, p < 0.05). NO production was markedly reduced in irradiated compared to non‐irradiated vessels, but was partially restored with MnTBAP (10 −4 M, SOD mimetic), as assessed by fluorescence microscopy with the NO‐specific dye DAF‐FM (213 ± 4, 160 ± 15, and 198 ± 12 fluorescence units, respectively; p < 0.05). Papaverine (an endothelium‐independent dilator) induced a similar dose‐dependent dilation of irradiated and non‐irradiated vessels (82 ± 2% vs. 88 ± 4% at 10 −4 M, respectively; n = 3, p = ns). We conclude that radiation impairs endothelium‐dependent dilation via NO reduction by ROS. These findings support a role for antioxidants in prevention of vascular complications during abdominal radiation therapy. This study was supported by the American Heart Association and the Crohn's & Colitis Foundation of America.