Effects of nitric oxide on leukocyte behavior in the angiogenic tumor microvessels

摘要

Using an experimental tumor model developed by the authors, intravital microscopic observations of the angiogenic processes in the mesenteric microvasculature and the hemodynamics of the newly formed microvessels were performed. In this model, tumor growth accompanying a marked angiogenesis was microscopically observable for up to 10 days. The length of the microvessels showed a significant increase in the tumor-bearing mesentery. In the newly formed tumor vessels, rolling and adherence of leukocytes in venules were both attenuated as compared in the normal mesenteric venules. To elucidate the mechanisms of this altered behavior of hemodynamics, the role of nitric oxide (NO) in regulating leukocyte dynamics in the tumor microcirculation was examined. Reduction of the baseline levels of leukocyte-endothelial cell interactions observed in the tumor venules were markedly attenuated by inhibition of NO synthase (NOS). These increases were neither found hi the tumor-free rats nor in normal microvessels of the tumor-bearing rats. These results suggest that an excessive production of NO in the tumor tissues create the tumor-specific microenvironment, thereby modulating leukocyte behavior in the angiogenic tumor vessels.