Effect of tachykinin NK2 receptor blockade on detrusor hyperreflexia induced by bacterial toxin in rats

被引:29
作者
Lecci, A [1 ]
Tramontana, M [1 ]
Giuliani, S [1 ]
Criscuoli, M [1 ]
Maggi, CA [1 ]
机构
[1] Menarini Ric Direzione Discovery, Pharmacol Res Dept, I-50131 Florence, Italy
关键词
tachykinin antagonist; MEN 11,420; SR 140,333; capsaicin; endotoxin; urinary bladder; micturition reflex;
D O I
10.1016/S0022-5347(01)63091-X
中图分类号
R5 [内科学]; R69 [泌尿科学(泌尿生殖系疾病)];
学科分类号
1002 ; 100201 ;
摘要
Purpose: To see whether a recently characterized model of bacterial toxin-induced urinary bladder inflammation (Stein et al., J. Urol. 155, 1133-1138, 1996) is associated with detrusor hyperreflexia, and whether endogenous tachykinins acting through NK2 or NK1 receptors were involved in this model. Materials and Methods: The bladder of urethane-anesthetized male Wistar rats was cannulated through the dome. Intravesical administration of protamine sulfate (PS, 10 mg./ml./rat) or vehicle for 1 hour was followed by the intravesical administration off, coli lipopolysaccharide (LPS, 1 mg./ml./rat) or vehicle for 1 hour. Cystometries (50 mu l./min.) were performed 3.5 hours after the exposure to LPS. MEN 11,420, a peptide tachykinin NK2 receptor antagonist, was administered before cystometries or, in a separate group of animals, during cystometries. The effect of SR 140,333, a non-peptide NK1, receptor antagonist, was also assessed in the presence or absence of MEN 11,420. The urodynamic effects of PS + LPS were also tested in capsaicin-pretreated rats. Results: Unlike PS or LPS alone, the intravesical administration of PS + LPS induced detrusor hyperreflexia. In PS + LPS treated animals during nonstop cystometries, the intermicturition interval was decreased by about 50% as compared to vehicle-pretreated rats. A quantitatively similar reduction in the bladder capacity was also observed. MEN 11,420 (100 nmol./kg., i.v.) restored the intermicturition interval in PS + LPS-pretreated rats at the level of controls by increasing the bladder capacity, whereas it had no effect in vehicle-pretreated rats. SR 140,333 (1 mu mol./kg., i.v.) neither modified urodynamic parameters in controls and in PS + LPS-treated rats nor altered the effect of MEN 11,420 in these groups. Capsaicin pretreatment (164 mu mol./kg., s.c., 4-5 days before) induced a two-fold increase of the bladder capacity in control rats and prevented PS + LPS-induced bladder hyperreflexia. Conclusions: The intravesical administration of PS + LPS produces the activation of capsaicin-sensitive afferents. Endogenous tachykinins released from these fibers act through NK2 receptors to induce detrusor hyperreflexia.
引用
收藏
页码:206 / 209
页数:4
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