EFFECT OF BRADYKININ AND TACHYKININ RECEPTOR ANTAGONIST ON XYLENE-INDUCED CYSTITIS IN RATS

The effects of the bradykinin receptor selective antagonist, Hoe 140, and of the tachykinin NK-1 receptor antagonist (+/-)CP 96,345 were investigated in a rat model of chemically-induced cystitis (intravesical instillation of xylene in female rats). Intravenous injection of bradykinin (1 mumol./kg.) or substance P (3 nmol./kg.) produced plasma protein extravasation (PPE) in the rat urinary bladder. Bradykinin response was prevented by Hoe 140 (100 nmol./kg. intravenously) and unaffected by (+/-)CP 96,345 (10 mumol./kg. intravenously). Plasma protein extravasation produced by substance P was inhibited by (+/-)CP 96,345 but unchanged by Hoe 140. Catheterization required for intravesical xylene instillation into the female rat bladder produced per se an inflammatory response which was abolished by either Hoe 140 or (+/-)CP 96,345. Intravesical instillation of xylene produced a large PPE response which was reduced by about 65% by Hoe 140 or (+/-)CP 96,345. Combined administration of the two antagonists produced an additive effect on the PPE response to xylene. We conclude that both bradykinin and tachykinins are involved in the inflammatory reaction of the rat urinary bladder to catheterization and xylene irritation.