Nitric oxide modulation of early angiogenesis.

Angiogenesis is the process of new vessel formation from an existing vasculature network. In all but a few circumstances it is tightly controlled and suppressed. Precise understanding of the factors involved in modulation of angiogenesis has significant potential clinical value. One agent believed to play a role in angiogenesis is nitric oxide. However, there remain substantial uncertainties concerning the specifics of this role. The present study was undertaken to better define the role nitric oxide plays in angiogenesis associated with acute wound healing. Muscle biopsies from the pectoralis major of C57B6 mice were embedded in 500 microl of type I collagen matrix, and incubated in the presence of growth medium for 14 days. Treatment wells received L-Arginine (2 mM), L-NAME (300 microM), or SNAP (10-20 microM). Angiogenic response was quantified as the measure of cell migration through the matrix and as the total cells recovered from the matrix. Whole lung specimens and aortic segments served as sources of endothelial and vascular smooth muscle cells respectively for proliferation studies under similar treatment conditions. Nitric oxide was found to exert either a stimulatory or inhibitory effect on angiogenesis and cell proliferation that was subject to the assay system and specific vascular cell types present. These results suggest that the role of nitric oxide in angiogenesis is context dependent. Copyright 2004 Wiley-Liss, Inc.