Role of nitric oxide in modulating permeability of hamster cheek pouch in response to adenosine 5′-diphosphate and bradykinin

The goal of this study was to determine the role of the synthesis and release of nitric oxide in modulating alterations in microvascular permeability of the hamster cheek pouch in response to adenosine 5′-diphosphate and bradykinin. We used intravital fluorescent microscopy to examine the permeability of the hamster cheek pouch to agonists before and following application of enzymatic inhibitors of nitric oxide, N^G-monomethyl-l-arginine (l-NMMA; 0.01, 0.1, and 1.0 μM) and N^w-nitro-l-arginine methyl ester (l-NAME; 0.01, 0.1, and 1.0 μM). Increases in permeability of the hamster cheek pouch were quantitated by the formation of microvascular leaky sites. ADP and bradykinin produced an increase in the number of venular leaky sites, and superfusion of l-NMMA and l-NAME significantly decreased ADPand bradykinin-induced increases in microvascular permeability. To determine the specificity of nitric oxide blockade on microvascular permeability, we examined changes in permeability in response to adenosine, and examined the effects of d-NMMA on microvascular permeability. Adenosine-induced increases in permeability were not altered by treatment with l-NMMA, and d-NMMA did not inhibit ADP-induced increases in microvascular permeability. Thus, these findings suggest that production of nitric oxide, in response to application of ADP and bradykinin, has a role in modulating macromolecular permeability of the hamster cheek pouch in vivo.