Early changes in L-arginine-nitric oxide metabolic pathways in response to the whole-body gamma irradiation of rats

Purpose: Nitric oxide (NO), a reactive radical, is formed in higher amounts from L-arginine by inducible NO synthase (iNOS) during early response to ionizing radiation presumably as a part of signal transduction pathways. This study investigated the changes in L-arginine-NO metabolic pathways within a 24-hour period after whole-body gamma irradiation of rats with the range of low to supra-lethal doses. Materials and methods: Young adult female Wistar rats received either 0–50 Gy whole-body irradiation or an intraperitoneal injection of bacterial lipopolysaccharide (LPS, 10 mg/kg). Exhaled NO was monitored using chemiluminiscence, nitrite + nitrate (NO_x) and L-arginine were assayed by high-performance liquid chromatography, and expression of iNOS was determined using Western blot. Results: Irradiation resulted in a dose-dependent increase of plasma NO_x to maximum levels which were 4-fold higher compared to controls (p < 0.001). The NO_x levels increased less in the bronchoalveolar lavage fluid (BAL) (1.7-fold, p < 0.001) and liver homogenate (2.5-fold, p < 0.05), respectively, and were dose-independent. Exhaled NO, lung NO_x, plasma and BAL L-arginine, and the expression of iNOS in lung and liver tissues of irradiated rats and controls were similar. LPS caused a considerable increase (p < 0.001) in exhaled NO (61-fold), NO_x levels (plasma 34-fold, BAL 6-fold, lung 5-fold, liver 4-fold), and in iNOS expression, respectively. Conclusion: In contrast to the LPS treatment of rats, the radiation-induced changes in L-arginine-NO metabolic pathways are modest, particularly in the airways and lungs. Noninvasive measurement of exhaled NO within a 24-h period following the exposure of rats to ionizing radiation has no value for biodosimetry. (authors)