Determination of angiogenesis-regulating properties of NO

Most used in vivo bioassay in laboratory is the rabbit cornea assay. Because the cornea is an avascular tissue, this assay avoids the problems of interpretation inherent in the other bioassays, such as the chick chorion allantoic membrane (CAM). The outgrowth of new vessels into the cornea stroma can be readily identified and their morphology documented. The corneal assay is performed in New Zealand white rabbits. Nitric oxide (NO) directs endothelial cells in each step of angiogenesis and its role is twofold. In vitro administration of NO donor drugs to sparse coronary endothelium increases their mitotic index and favors cell migration and matrix degradation. As a result, in vivo NO donors speed up and potentiate neovascular growth. Thus, NO acts as the true effector of angiogenesis. However, mediators of angiogenesis signal the angiogenic switch in endothelium by releasing free NO and elevating cGMP levels. The development of NO-targeting drugs with higher selectivity for the different isoforms, combined with targeted tissue delivery to minimize side effects, as well as qualitative assessment of NO function from activity, to genomic expression, is a promising strategy for the exploitation of the findings on the role of NO on angiogenesis