Models of Urogenital Dysfunction: Assessment of Volume‐Evoked Micturition Reflex (VEMR) in the Conscious Rat by Cystometry

Philip Nunn1, Ian Williamson1, Donald Newgreen1, Mark Bushfield2

1 Discovery Biology, Pfizer Central Research, Sandwich Kent, United Kingdom, 2 Cambridge Drug Discovery, Cambridge, United Kingdom
Publication Name:  Current Protocols in Pharmacology
Unit Number:  Unit 5.12
DOI:  10.1002/0471141755.ph0512s02
Online Posting Date:  May, 2001
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Abstract

This unit describes a conscious rat model that allows the investigation of compounds administered by various routes (e.g., oral, intravenous and subcutaneous). This procedure can be used to examine the effects of agents on supraspinal, spinal and peripheral control of the micturition reflex, in addition to effects on parasympathetic neurotransmission and detrusor relaxation. One advantage to this procedure over anesthetized dog and rat models is the ability to determine pharmacological effects in the absence of possible interfering effects of anesthetics.

     
 
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Table of Contents

  • Reagents and Solutions
  • Commentary
  • Figures
  • Tables
     
 
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Materials

Basic Protocol 1:

  Materials
  • 200‐ to 300‐g male caesarean‐derived Sprague‐Dawley rats (presurgery weight; Charles River Labs)
  • 50 µg/ml Sublimaze (fentanyl; Janssen Pharmaceuticals)
  • 1 mg/ml Domitor (medetomidine HCl; Orion)
  • 10% (v/v) Hibitane (ICI Pharmaceuticals) in 70% ethanol (store up to 1 month at room temperature)
  • 0.9% (w/v) NaCl, sterile
  • 50 U/ml heparin in sterile 0.9% NaCl (store up to 1 month at room temperature)
  • 1 mg/ml Antisedan (atipamezole HCl; Orion)
  • 10 mg/ml Nubain (nalbuphine HCl; DuPont)
  • Test compound solutions (see recipe)
  • 60 mg/ml sagatal (pentabarbitone sodium; B.P.; Rhone Merieux) or a CO 2 chamber
  • Electric razor
  • Autoclaved dissection instruments
  • Bladder catheter: 250‐mm polyethylene‐100 (PE‐100) tubing (0.86‐mm i.d., 1.52‐mm o.d.) with one end heated to create a small flange
  • 2.0 and 4.0 silk ligature
  • Surgical trocar and cannula (280‐mm length, slightly curved, 2‐mm i.d.)
  • 17‐G single‐use intravenous cannula (Luer fitting, ref 200/500/030; 1.4‐mm o.d.; 0.6‐mm i.d.; Portex)
  • Dual‐connection sealable Teflon fistula with screw top (specially designed; see step annotation)
  • Restraining cages (made in house; see Yaksh et al., )
  • Infusion pump (B. Braun, Unita S, type 871044/9)
  • Pressure transducer (Ohmeda Catheter Products, P23XL‐1)
  • Polygraph recorder (Grass or equivalent)
  • On‐line data capture and analysis system (e.g., MacLab, AD Instruments)
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Figures

Videos

Literature Cited

Literature Cited
   Conte, B., D'Aranno, V., Santicioli, P., Giuliani, S., Mancinelli, A., Furio, M., Maggi, C.A., and Meli, A. 1988. New method for recording cysto‐metrograms in conscious, freely moving rats. J. Pharmacol. Methods 19:57‐61.
   Guan, Z., Kiruluta, G., Coolsaet, B., and Elhilali, M. 1995. A minipig model for urodynamic evaluation of infravesical obstruction and its possible reversibility. J. Urol. 154:580‐586.
   Guarnari, L., Ibba, M., Angelico, P., and Testa, R. 1991. Effects of Oxybutynin, Terodiline, and Nifedipine on the cystometrogram in conscious rats with infravesical outflow obstruction. Pharmacol. Res. 24:263‐272.
   Hu, C., Flecknell, P.A., and Liles, J.H. 1992. Fentanyl and medetomidine in the rat and its reversal using atipamezole and either nalbuphine or butorphanol. Lab. Anim. 26:15‐22.
   Metcalfe, M., Bushfield, M., Naylor, A.M., and Templeton, D. 1994. Tachykinin‐activated bladder contractions in the anaesthetised guinea‐pig. Br. J. Pharmacol. 112:563P.
   Morikawa, K., Kakiuchi, M., Yamauchi, T., Hashimoto, S., Sawada, Y., Kato, H., and Ito, Y. 1989a. Pharmacological studies on the micturition reflex (1): Effects of various drugs on bladder function in rats. Pharmacometrics 37:17‐26.
   Morikawa, K., Kakiuchi, M., Yamauchi, T., Hashimoto, S., Sawada, Y., Kato, H., and Ito, Y. 1989b. Pharmacological studies on the micturition reflex (2): Effects of various drugs on bladder function and urethral functions in rats and dogs. Pharmacometrics 37:27‐37.
   Williamson, I.J.R., Newgreen, D.T., Bushfield, M., and Naylor, A.M. 1996. The effects of the GABAB agonists baclofen and 3‐APPi on micturition parameters in a conscious rat cystometry model. Br. J. Pharmacol. 119:201P.
   Yaksh, T.L.C., Durant, P.A., and Brent, C.R. 1986. Micturition in rats: A chronic model for study of bladder function and effects of anaesthetics. Am. J. Physiol. 251:1177‐1185.
Key Reference
   Yaksh et al., 1986. See above.
  Cystometry model on which this unit is based. Variations presented in this unit improve the procedure for the animals and consequently improve the quality of the cystometrography results. The main changes are as follows: both bladder and venous catheters are implanted in a single surgical procedure, the animals are given at least 72 hr postsurgery for recovery, and sealable fistulae are used, which allow the animals to move freely in their home cage between cystometry studies.
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