IN-VIVO EXPERIMENTAL-EVIDENCE THAT THE NITRIC-OXIDE PATHWAY IS INVOLVED IN THE X-RAY-INDUCED ANTIANGIOGENICITY

We have investigated both the effects of X-rays on angiogenesis and th e possible role of nitric oxide (NO) on the observed antiangiogenic ef fect of X-rays, using as an in vivo model the chick embryo chorioallan toic membrane (CAM). These effects were assessed both morphologically and biochemically, by measuring vascular density and collagenous prote in biosynthesis, respectively, on days 9 and 14 of the chick embryo de velopment. Vascular density and cytoxicity of the CAM were also evalua ted histologically. We have shown that X-rays have an antiangiogenic e ffect on the system used and that the NO synthase inhibitor N-G-nitro- L-arginine methyl ester (L-NAME) promoted angiogenesis of the non-irra diated CAM and reversed the antiangiogenic effect of irradiation. D-NA ME, which is an inactive enantiomer of L-NAME, showed no such effects. L-Arginine, which is the substrate for NO synthase, had a modest anti angiogenic effect on the non-irradiated CAM, no effect on the irradiat ed CAM and abolished the angiogenic effect of L-NAME on these CAM prep arations. These results suggest that NO is involved in the antiangioge nic mechanism of X-rays and that pharmacological manipulation of NO fi rstly, may offer a better understanding of these mechanisms and, secon dly, may also prove to be an alternative therapeutic approach for trea ting pathological conditions involving angiogenesis.