EFFECT OF TACHYKININ NK2 RECEPTOR BLOCKADE ON DETRUSOR HYPERREFLEXIA INDUCED BY BACTERIAL TOXIN IN RATS

Purpose: To see whether a recently characterized model of bacterial to xin-induced urinary bladder inflammation (Stein et al., J. Urol. 155, 1133-1138, 1996) is associated with detrusor hyperreflexia, and whethe r endogenous tachykinins acting through NK2 or NK1 receptors were invo lved in this model. Materials and Methods: The bladder of urethane-ane sthetized male Wistar rats was cannulated through the dome. Intravesic al 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. Cystome tries (50 mu l./min.) were performed 3.5 hours after the exposure to L PS. MEN 11,420, a peptide tachykinin NK2 receptor antagonist, was admi nistered before cystometries or, in a separate group of animals, durin g 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-pre treated rats. Results: Unlike PS or LPS alone, the intravesical admini stration of PS + LPS induced detrusor hyperreflexia. In PS + LPS treat ed animals during nonstop cystometries, the intermicturition interval was decreased by about 50% as compared to vehicle-pretreated rats. A q uantitatively similar reduction in the bladder capacity was also obser ved. MEN 11,420 (100 nmol./kg., i.v.) restored the intermicturition in terval in PS + LPS-pretreated rats at the level of controls by increas ing the bladder capacity, whereas it had no effect in vehicle-pretreat ed 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 ef fect 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 bladd er capacity in control rats and prevented PS + LPS-induced bladder hyp erreflexia. Conclusions: The intravesical administration of PS + LPS p roduces the activation of capsaicin-sensitive afferents. Endogenous ta chykinins released from these fibers act through NK2 receptors to indu ce detrusor hyperreflexia.