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 inv estigated in a rat model of chemically-induced cystitis (intravesical instillation of xylene in female rats). Intravenous injection of brady kinin (1 mumol./kg.) or substance P (3 nmol./kg.) produced plasma prot ein extravasation (PPE) in the rat urinary bladder. Bradykinin respons e was prevented by Hoe 140 (100 nmol./kg. intravenously) and unaffecte d by (+/-)CP 96,345 (10 mumol./kg. intravenously). Plasma protein extr avasation 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 inflammat ory response which was abolished by either Hoe 140 or (+/-)CP 96,345. Intravesical instillation of xylene produced a large PPE response whic h was reduced by about 65% by Hoe 140 or (+/-)CP 96,345. Combined admi nistration of the two antagonists produced an additive effect on the P PE response to xylene. We conclude that both bradykinin and tachykinin s are involved in the inflammatory reaction of the rat urinary bladder to catheterization and xylene irritation.