LOOP DIURETICS ATTENUATE BRADYKININ-INDUCED INCREASE IN CLEARANCE OF MACROMOLECULES IN THE ORAL-MUCOSA

The purpose of this study was to determine whether loop diuretics atte nuate bradykinin-induced increase in clearance of macromolecules in th e oral mucosa in situ and, if so, to start to determine the mechanisms that mediated these responses. By using intravital microscopy, we fou nd that bradykinin induced a significant concentration-dependent incre ase in fluorescein isothiocyanate-labeled dextran (mel mass 70 kDa) le aky site formation in the hamster cheek pouch. These responses were si gnificantly attenuated by topical application of two structurally dist inct loop diuretics, furosemide and ethacrynic acid, onto the cheek po uch (P < 0.05). Hydrochlorothiazide, a nonloop diuretic, had no signif icant effects on bradykinin-induced responses. Furosemide had no signi ficant effects on adenosine-induced leaky site formation. Application of bradykinin after furosemide, but not after hydrochlorothiazide, was associated with a significant concentration-dependent decrease in bra dykinin-like immunoreactivity in the cheek pouch suffusate (P < 0.05). Prostaglandins and changes in vasomotor tone did not modulate the eff ects of furosemide on bradykinin-induced responses. These data indicat e that loop diuretics attenuate bradykinin-induced increase in clearan ce of macromolecules in the oral mucosa in a specific fashion, probabl y by amplifying local bradykinin catabolism. We suggest that topical l oop diuretics could be useful in the treatment of oral mucosa inflamma tion elicited by bradykinin.