PURIFIED ACE ATTENUATES SMOKELESS TOBACCO-INDUCED INCREASE IN MACROMOLECULAR EFFLUX FROM THE ORAL-MUCOSA

The purpose of this study was to determine whether purified angiotensi n I-converting enzyme (ACE) attenuates smokeless tobacco extract (STE) induced increase in macromolecular efflux from the in situ oral mucosa . By using intravital microscopy, we found that; suffusion of an aqueo us extract of smokeless tobacco elicited significant concentration-dep endent leaky site formation and increase in clearance of fluorescein i sothiocyanate-labeled dextran (mel mass, 70 kDa) from the hamster chee k pouch (P < 0.05). Suffusion of purified rabbit lung ACE significantl y attenuated these responses in a concentration-dependent fashion (P < 0.05). These effects were specific because purified ACE also signific antly attenuated the increase in macromolecular efflux elicited by bra dykinin, which is produced in the cheek pouch during suffusion of STE, but did not attenuate the increase elicted by adenosine. Moreover, su ffusion of heat-inactivated purified ACE and purified superoxide dismu tase had no significant effects on STE- and bradykinin-induced respons es. Collectively, these data suggest that exogenous ACE attenuates STE -induced increase in macromolecular efflux from the in situ oral mucos a, in part, by promoting local bradykinin catabolism.