MECHANISMS OF SMOKELESS TOBACCO-INDUCED ORAL-MUCOSA INFLAMMATION - ROLE OF BRADYKININ

The purpose of this study was to determine whether an aqueous extract of smokeless tobacco (moist snuff increases clearance of macromolecule s from postcapillary venules in the in situ oral mucosa and, if so, wh ether bradykinin mediated this response, Using intravital microscopy, we found that 20-min suffusion of the extract elicited significant con centration-dependent leaky site formation and increase in clearance of FITC-dextran (molecular mass, 70 kDa) from the hamster cheek pouch (p < 0.05), These responses were associated with a significant increase in bradykinin-like immunoreactivity in the suffusate. Smokeless tobacc o extract-induced leaky site formation and increase in clearance of FI TC-dextran were significantly attenuated by NPC 17647 and Hoe 140 (p < 0.05), two bradykinin B-2 receptor antagonists, but not by desArg(9), [Leu(8)]bradykinin, a bradykinin B-1 receptor antagonist, Both bradyki nin B-2 receptor antagonists had no significant effects on adenosine-i nduced responses. Indomethacin had no significant effects on smokeless tobacco extract-induced responses, Exposure to smokeless tobacco extr act was associated with a significant decrease in angiotensin I-conver ting enzyme activity and a small, but significant, increase in neutral endopeptidase 24.11 activity in the cheek pouch, two peptidases widel y distributed in the microcirculation that cleave and inactivate brady kinin (p < 0.05), Overall, these data suggest that smokeless tobacco e licits plasma exudation in the oral mucosa in vivo in a specific fashi on, and that this response is mediated by bradykinin.