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Effect of tachykinin NK2 receptor blockade on detrusor hyperreflexia induced by bacterial toxin in rats.
- Source :
-
The Journal of urology [J Urol] 1998 Jul; Vol. 160 (1), pp. 206-9. - Publication Year :
- 1998
-
Abstract
- 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.<br />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 of E. coli lipopolysaccharide (LPS, 1 mg./ml./rat) or vehicle for 1 hour. Cystometries (50 microl./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.<br />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 micromol./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 micromol./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.<br />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.
- Subjects :
- Animals
Male
Muscle, Smooth drug effects
Muscle, Smooth physiopathology
Piperidines pharmacology
Protamines pharmacology
Quinuclidines pharmacology
Rats
Rats, Wistar
Escherichia coli
Lipopolysaccharides
Peptides, Cyclic pharmacology
Receptors, Tachykinin antagonists & inhibitors
Reflex, Abnormal drug effects
Urinary Bladder drug effects
Urinary Bladder physiopathology
Subjects
Details
- Language :
- English
- ISSN :
- 0022-5347
- Volume :
- 160
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- The Journal of urology
- Publication Type :
- Academic Journal
- Accession number :
- 9628651