Abstract
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=<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.
Original language | English (US) |
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Pages (from-to) | 287-294 |
Number of pages | 8 |
Journal | Arteriosclerosis, thrombosis, and vascular biology |
Volume | 26 |
Issue number | 2 |
DOIs | |
State | Published - Feb 2006 |
Keywords
- 2′, 7′-dichlorodihydrofluorescein diacetate
- Dihydroethidine
- Endothelial dysfunction
- Microvessels
- Radiation
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine