The stable vip analog, ro 24-9981, potentiates bradykinin-induced
increases in clearance of macromolecules.
Gao, Xiao-Pei, and Israel Rubinstein.
Department of Medicine, University of Illinois at Chicago, and West
Side Department of Veterans Affairs Medical Center, Chicago, Illinois
60612-7323
APStracts 2:0186H, 1995.
The purpose of this study was to determine whether the stable cyclic
peptide analog 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 (m.w.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.
Received 25 February 1994; accepted in final form 27 April 1995.
APS Manuscript Number H187-4.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 9 May 1995.