Abstract 5460: Promoting Effect of 188 Re Radiation on the L-arginine/nitric Oxide Pathway in the Balloon Injured Rat Abdominal Aortic Arteries

Abstract

This study examined the effect of 188 Re radiation on L-Arginine(L-Arg)/NO pathway in the injured rat abdominal aortic artery and investigated the mechanism involved. Forty-three rats were randomly divided into 4 groups: control (n=10), 14 days after balloon injury without treatment (14B, n=10), 14 days after balloon injury plus radiation (14BR, n=13), radiation only (SR, n=10). Vascular lesions were created in the abdominal aortic arteries by overstretch balloon injury. Arteries were then left untreated or were treated with intra-aortic beta-radiation using 188 Re balloon to deliver 20Gy at 2 mm from the center of the source. Intima/medium(I/M) ratio of the artery were evaluated. Plasma NO, aortic NO generation, L-Arg transport, iNOS activity, iNOS mRNA and protein expression were studied. We found that I/M ratio in 14B group was higher than control (0.558±0.175 vs0.063±0.010, P<0.01), and higher than that in 14BR group (0.080±0.021, P<0.01). Plasma NO in each group was not significantly different with each other. NO generated by aortic artery in 14B group were 177% (P<0.01) higher than control (8.65±2.47μmol/mg protein) and 17% (P<0.05) lower than that in 14BR group. iNOS activity in the 14B group was 44% (P<0.01) higher than control(180±22 pmol.mg protein −1 .min −1 ) and 11%(P<0.05) lower than that in 14BR group. Quantitative RT-PCR showed that iNOS mRNA in 14B group was 290% (P<0.01) higher than control and 19%(P<0.05) lower than that in 14BR group. Immunohistochemistry results showed no iNOS protein expression in control. iNOS protein were similarly expressed in the 14B and 14BR groups (P>0.05). However iNOS protein was strongly expressed in the SR group. Incubated in the KH solution with L-Arg(100μmol/L), L-Arg transport efficacy in 14B group was 248% (P<0.01)higher than control(1.04±0.15pmol.g protein −1 .min −1 ), and 39%(P<0.01) higher than that in 14BR group. In summary, we found 188 Re inhibited neointima hyperplasia and promoted NO generation, iNOS activity and iNOS mRNA expression in the injured artery. However, it decreased L-Arg transport and had no significant influence on iNOS protein expression in the injured artery. Therefore, effect of radiation on the L-Arg/NO pathway explains partly the mechanism of intracoronary radiation.