Ovalbumin-induced neurogenic inflammation in the bladder of sensitized rats.
1. We have developed and characterized a model of immediate hypersensitivity/inflammation of the urinary bladder in vivo induced by local application of ovalbumin (OA) in OA- sensitive female rats. Two parameters of the inflammatory response were assessed following OA challenge: plasma protein extravasation (PPE) and changes in smooth muscle reactivity. The former was estimated by measurement of Evans blue extravasation at 0.5, 2, 4, 8 and 24 h time point following in vivo challenge. Changes in reactivity were determined by measurement of isotonic tension responses of urinary bladder strips following OA challenge in vitro. 2. Acute in vivo intravesical OA challenge (10 mg in 0.3 ml saline) in actively sensitized female Wistar rats caused a time-dependent PPE in the urinary bladder which was biphasic with peak responses at 2-4 and 24 h. 3. The PPE response to acute OA challenge, above base-line, at 2 h was abolished by systemic capsaicin pretreatment (50 mg kg(-1), s.c., 4 days before use) (P < 0.05) whilst the response at 24 h was unaffected. The 2 h time point was then used for further studies. 4. Degranulation of mast cells, achieved by pretreatment with compound 48/80 (5 mg kg(-1), s.c. for 3 consecutive days), completely abolished the PPE response to OA challenge at the 2 h time point. 5. The tachykinin NK1 receptor antagonist, SR 140333 (0.1 micromol kg(-1), i.v.), abolished the 2 h PPE response whilst the tachykinin NK2 receptor antagonist MEN 11420 (0.1 micromol kg(-1), i.v.) appeared to reduce the response by approximately 50% but this did not reach significance. The bradykinin B2 receptor antagonist, Hoe 140 (0.1 micromol kg(-1), i.v.), similarly to SR 140333, blocked the 2 h PPE response to OA, whereas the selective B1 receptor antagonist B 9858 (0.1 micromol kg(-1), i.v.) had no significant effect. Inhibition of cyclo-oxygenase (COX) achieved by pretreatment with the COX inhibitor dexketoprofen (5.3 micromol kg(-1), i.v.) also blocked the PPE response, whilst the leukotriene receptor antagonist ONO 1078 (1 micromol kg(-1), i.v.) significantly reduced PPE by about 80%. 6. In the rat isolated urinary bladder OA (1 mg ml(-1)) challenge produced a biphasic response with a rapidly achieved maximal contraction followed by a sustained contraction for approximately 25 min. In vitro capsaicin pretreatment (10 microM for 15 min) significantly attenuated the duration of the sustained contraction whilst having no effect on the maximum contractile response achieved. In vivo pretreatment of animals with compound 48/80 significantly attenuated (42%) the maximum contractile response. Combination of both treatments almost completely abolished the response. In vitro treatment with Hoe 140 (1 microM) had no significant effect on the response to OA and neither did ONO 1078 (1 microM). 7. These results show that both the early inflammatory response and alterations in smooth muscle reactivity to OA challenge in actively sensitized animals are dependent on mast cell degranulation and the activation of sensory C-fibres. Furthermore this model of allergic cystitis may be useful for investigating both the processes involved and potential novel therapies in the treatment of interstitial cystitis.
Ahluwalia
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Centre for Clinical Pharmacology, The Rayne Institute, University College London.
Giuliani
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Scotland
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Maggi
C A
CA
D000818:Animals; D001798:Blood Proteins / Q000378:metabolism; D003556:Cystitis / Q000139:chemically induced* / Q000378:metabolism / Q000503:physiopathology; D004195:Disease Models, Animal; D005260:Female; D066298:In Vitro Techniques; D009130:Muscle, Smooth / Q000503:physiopathology; D010047:Ovalbumin / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D001750:Urinary Bladder, Neurogenic / Q000139:chemically induced* / Q000378:metabolism / Q000503:physiopathology
D001798:Blood Proteins; D010047:Ovalbumin