The stable VIP analogue, Ro 24-9981, potentiates bradykinin-induced increases in clearance of macromolecules.

The purpose of this study was to determine whether the stable cyclic peptide analogue of human vasoactive intestinal peptide, Ro 24-9981, modulates bradykinin-induced plasma exudation in the oral mucosa and if so, to determine the mechanisms that mediated these responses. Using intravital microscopy, we found that suffusion of Ro 24-9981 had no significant effects on leaky site formation and clearance of fluorescein-isothiocyanate-dextran (mol mass 70 kDa) in the hamster cheek pouch. However, Ro 24-9981 significantly potentiated bradykinin-induced increases in leaky site formation and clearance of fluorescein-isothiocyanate-dextran (P < 0.05). These effects were specific because Ro 24-9981 had no significant effects on adenosine and calcium ionophore A23187-induced increases in leaky site formation and clearance of fluorescein-isothiocyanate-dextran. Furthermore, they were not mediated by cyclooxygenase products of arachidonic acid metabolism because indomethacin was ineffective. NG-nitro-L-arginine methyl ester, a selective inhibitor of nitric oxide synthase, but not NG-nitro-D-arginine methyl ester, significantly attenuated the effects of both bradykinin and Ro 24-9981 with bradykinin (P < 0.05). These responses were restored by L-arginine but not D-arginine. Collectively, these data indicate that bradykinin-induced plasma exudation in the oral mucosa was potentiated by Ro 24-9981 in a specific receptor-mediated fashion. These responses were mediated, in part, by the L-arginine/nitric oxide biosynthetic pathway.