Giuliani S, Santicioli P, Lippe I T, Lecci A, Maggi C A
Pharmacology Department, A. Menarini Pharmaceuticals, Florence, Italy.
J Urol. 1993 Sep;150(3):1014-7. doi: 10.1016/s0022-5347(17)35677-x.
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.
在化学诱导膀胱炎的大鼠模型（雌性大鼠膀胱内滴注二甲苯）中，研究了缓激肽受体选择性拮抗剂Hoe 140和速激肽NK-1受体拮抗剂（+/-）CP 96,345的作用。静脉注射缓激肽（1 μmol./kg.）或P物质（3 nmol./kg.）可导致大鼠膀胱血浆蛋白外渗（PPE）。Hoe 140（静脉注射100 nmol./kg.）可阻止缓激肽反应，而（+/-）CP 96,345（静脉注射10 μmol./kg.）对其无影响。P物质引起的血浆蛋白外渗被（+/-）CP 96,345抑制，但不受Hoe 140影响。雌性大鼠膀胱内滴注二甲苯所需的插管本身会产生炎症反应，而Hoe 140或（+/-）CP 96,345均可消除该反应。膀胱内滴注二甲苯会产生较大的PPE反应，Hoe 140或（+/-）CP 96,345可使其降低约65%。两种拮抗剂联合给药对二甲苯引起的PPE反应产生相加作用。我们得出结论，缓激肽和速激肽均参与大鼠膀胱对插管和二甲苯刺激的炎症反应。
