Radiation induces endothelial dysfunction in murine intestinal arterioles via enhanced production of reactive oxygen species. Arterioscler Thromb Vasc Biol 2006 Feb;26(2):287-94
Date
12/03/2005Pubmed ID
16322529DOI
10.1161/01.ATV.0000198399.40584.8cScopus ID
2-s2.0-33644860459 (requires institutional sign-in at Scopus site) 64 CitationsAbstract
OBJECTIVE: Endothelial dysfunction and vascular dysregulation contribute to the pathological effects of radiation on tissues. The objectives of this study were to assess the acute effect of irradiation on acetylcholine (Ach)-induced dilation of gut submucosal microvessels.
METHODS AND RESULTS: Rats were exposed in vivo to 1 to 9 cGy in 3 fractions per week on alternate days for 3 successive weeks for a total dose of up to 2250 cGy. Submucosal microvessels were isolated after varying levels of irradiation. Diameters of isolated vessels were measured using videomicroscopy, and the dose-response relationship to Ach was determined. Dihydroethidine and 2', 7'-dichlorodihydrofluorescein diacetate fluorescent probes were used to assess reactive oxygen species (ROS) production. After constriction (30% to 50%) with endothelin, dilation to graded doses of Ach (10(-9)-10(-4) M) was observed in control vessels (maximal dilation [MD] 87+/-3%; n=7). However, Ach-induced dilation was reduced in vessels from irradiated rats (MD=3+/-9%; n=7; P= or <0.05 versus controls). Significant increases in superoxide and peroxides were observed in irradiated microvessels. Irradiated microvessels pretreated with superoxide dismutase-mimetic demonstrated significant improvement in Ach-induced vasodilation compared with irradiation alone, suggesting that superoxide contributes to impaired dilation to Ach after irradiation.
CONCLUSIONS: Radiation induces acute microvascular dysfunction in the resistance arterioles of the intestine. Enhanced ROS contribute to this dysfunction and therefore may represent a novel therapeutic target to minimize radiation toxicity in the gut.
Author List
Hatoum OA, Otterson MF, Kopelman D, Miura H, Sukhotnik I, Larsen BT, Selle RM, Moulder JE, Gutterman DDAuthor
Mary F. Otterson MD Professor in the Surgery department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AcetylcholineAnimals
Arterioles
Cyclic N-Oxides
Endothelium, Vascular
Free Radical Scavengers
Intestines
Metalloporphyrins
Nitric Oxide
Radiation Injuries, Experimental
Radiation-Protective Agents
Rats
Rats, Sprague-Dawley
Reactive Oxygen Species
Spin Labels
Vascular Diseases
Vasodilation
Vasodilator Agents