title: Effect of dexamethasone on cyclophosphamide-induced cystitis in rats: lack of relation with bradykinin B1 receptor-mediated motor responses.
abstract: We investigated the role of bradykinin B receptors in inducing urinary bladder contraction and maintaining bladder compliance in anaesthetized rats following cyclophosphamide-induced bladder inflammation and the influence of dexamethasone treatment on these responses. In the group treated with cyclophosphamide the amplitude of the contraction induced by the selective bradykinin B1 receptor agonist des-Arg9-bradykinin was larger than that in controls and dexamethasone prevented the up-regulation of this response induced by inflammation. The specific binding of [3H]des-Arg10-kallidin to bladder membranes was only detected in cyclophosphamide-treated rats: this binding was prevented by dexamethasone pretreatment. The bladder contraction induced by des-Arg9-bradykinin in cyclophosphamide-treated rats was antagonized by the bradykinin B1 receptor antagonist des-Arg9-D-Arg-[Hyp3,Thi5,D-Tic7,Oic8]bradykinin (des-Arg10-Hoe 140). Cyclophosphamide treatment increased the bladder weight and dexamethasone reversed this effect. Bladder compliance was decreased in the bladder inflammation group and this effect was partially reversed by dexamethasone pretreatment. Neither des-Arg10-Hoe 140 nor the combined administration of des-Arg10Hoe 140 and the selective bradykinin B2 receptor antagonist D-Arg-[Hyp3,Thi5,D-Tic7,Oic8]bradykinin (Hoe 140) affected bladder compliance, thus excluding a role of kinins in the maintenance of bladder tone during inflammation. These results indicate that: (1) dexamethasone pretreatment ameliorates cyclophosphamide-induced bladder inflammation: (2) dexamethasone pretreatment prevents cyclophosphamide-induced up-regulation of bradykinin B receptors; (3) kinins do not contribute to the increased vesical tone during inflammation.
authors: Pharmacology Department, Menarini Ricerche, Florence, Italy.
authors: A
authors: A
authors: Lecci
authors: S
authors: S
authors: Meini
authors: R
authors: R
authors: Patacchini
authors: M
authors: M
authors: Tramontana
authors: S
authors: S
authors: Giuliani
authors: M
authors: M
authors: Criscuoli
authors: C A
authors: CA
authors: Maggi
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001667:Binding, Competitive; D001920:Bradykinin / Q000031:analogs & derivatives / Q000494:pharmacology; D002273:Carcinogens / Q000009:adverse effects*; D003520:Cyclophosphamide / Q000009:adverse effects*; D003556:Cystitis / Q000139:chemically induced / Q000517:prevention & control*; D003907:Dexamethasone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D007609:Kallidin / Q000031:analogs & derivatives / Q000378:metabolism; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D011869:Radioligand Assay; D051381:Rats; D017208:Rats, Wistar; D043783:Receptor, Bradykinin B1; D018002:Receptors, Bradykinin / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D014316:Tritium; D001743:Urinary Bladder / Q000378:metabolism / Q000503:physiopathology
chemical_list: D000893:Anti-Inflammatory Agents; D002273:Carcinogens; D043783:Receptor, Bradykinin B1; D018002:Receptors, Bradykinin; D014316:Tritium; C024626:bradykinin, des-Arg(9)-; D007609:Kallidin; C052787:kallidin, des-Arg(10)-; D003907:Dexamethasone; D003520:Cyclophosphamide; D001920:Bradykinin