Summary We have investigated both the effects of X-rays on angiogenesis and the possible role of nitric oxide (NO) on the observed antiangiogenic effect of X-rays, using as an in vivo model the chick embryo chorioallantoic membrane (CAM). These effects were assessed both morphologically and biochemically, by measuring vascular density and collagenous protein biosynthesis, respectively, on days 9 and 14 of the chick embryo development. Vascular density and cytotoxicity of the CAM were also evaluated histologically. We have shown that X-rays have an antiangiogenic effect on the system used and that the NO synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME) promoted angiogenesis of the non-irradiated CAM and reversed the antiangiogenic effect of irradiation. D-NAME, which is an inactive enantiomer of L-NAME, showed no such effects. L-Arginine, which is the substrate for NO synthase, had a modest antiangiogenic effect on the nonirradiated CAM, no effect on the irradiated CAM and abolished the angiogenic effect of L-NAME on these CAM preparations. These results suggest that NO is involved in the antiangiogenic mechanism of X-rays and that pharmacological manipulation of NO firstly, may offer a better understanding of these mechanisms and, secondly, may also prove to be an alternative therapeutic approach for treating pathological conditions involving angiogenesis.

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Image-directed colour Doppler sonography has been successfully introduced for the detection of hepatic haemodynamic changes in the presence of liver metastases. The aim of our study was to correlate these haemodynamic changes with the liver histology at the time of measurement. We experimentally induced liver metastases in 30 male Wistar rats by inoculating Walker 256 tumour subcutaneously. The animals were assigned into three groups of ten and were studied sonographically at 4, 7 and 15 days after tumour implantation. Another group of ten normal animals were used as controls. Portal vein and hepatic artery measurements included resistance index (PVRI, HARI) and flow volume (PVFV, HAFV). Doppler perfusion index (DPI) of the liver was calculated as the ratio of HAFV/PVFV + HAFV. Liver histology followed each Doppler measurement. Metastases were first encountered on day 4, as small groups of cells in the connective tissue of the porta hepatis and the portal triads without apparent vascular association. Distinct elevation of HAFV and DPI was recorded in comparison with the controls (p = 0.0004 and p = 0.0005, respectively). PVFV reduction was subtle. Up to day 15 there were no significant changes in the measurements. Our data suggest that HAFV and DPI can efficiently detect early liver metastases and this is in accordance with existing clinical reports. Haemodynamic changes seem to originate from the early non-vascular phase of the metastases.

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