Models of Urogenital Dysfunction: Urinary Urge Incontinence (UUI) in Anesthetized Dog and Rat Models

Donald Newgreen1, Charles Anderson1, Philip Nunn1, Anthony Carter1, Mark Bushfield2

1 Discovery Biology, Pfizer Central Research, Kent, United Kingdom, 2 Cambridge Drug Discovery, Cambridge, United Kingdom
Publication Name:  Current Protocols in Pharmacology
Unit Number:  Unit 5.11
DOI:  10.1002/0471141755.ph0511s02
Online Posting Date:  May, 2001
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Abstract

This unit describes a model system for the measurement of the effects of compounds on bladder function in anesthetized dog and rat. A protocol is also described for measuring nerveā€stimulated salivary secretion which is particularly relevant when investigating agents that modulate parasympathetic drive (such as muscarinic antagonists), since it allows for the measurement of relative selectivity of bladder function over salivation. This unit describes a model system for the measurement of the effects of compounds on bladder function in anesthetized dog and

     
 
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Table of Contents

  • Basic Protocol 1: Measurement of Pelvic Nerve–Stimulated Bladder Contraction and Cardiovascular Function in the Anesthetized Dog
  • Alternate Protocol 1: Measurement of Pelvic Nerve–Stimulated Bladder Contraction and Cardiovascular Function in the Anesthetized Rat
  • Support Protocol 1: Measurement of Parasympathetic Nerve–Induced Salivary Secretion from the Submandibular Gland of the Dog
  • Reagents and Solutions
  • Commentary
  • Figures
  • Tables
     
 
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Materials

Basic Protocol 1: Measurement of Pelvic Nerve–Stimulated Bladder Contraction and Cardiovascular Function in the Anesthetized Dog

  Materials
  • 12.5‐ to 16‐kg male beagle
  • Piritramide (Janssen Pharmaceuticals)
  • 11% (w/v) urethane (ethyl carbamate; Sigma)
  • 100 mg/ml α‐chloralose (Sigma) in polyethylene glycol (PEG) 300
  • 0.9% (w/v) NaCl, sterile
  • Test compound solution (e.g., atropine; see recipe)
  • Saturated KCl solution
  • Angiocath
  • Unita S syringe pump (B. Braun Medical)
  • Endotracheal tube, size 9
  • Laryngoscope
  • Large thermostatically controlled operating table
  • Respirator (Ugo Basile dog respiratory pump; Linton Instrumentation)
  • Expired air analyzer (Datex Normocap 200; Instrumentarium)
  • Electric shaver
  • Cautery (Engel‐Löter, 100S)
  • Cannulae (nonsterile tubing; Portex):
  •  pp240 (coded 800/100/460/100; 1.67‐mm i.d., 2.42‐mm o.d.)
  •  pp100 (coded 800/100/280/100; 0.86‐mm i.d., 1.52‐mm o.d.)
  •  dog bladder cannula 6FG (coded 303/800/060; 2.1‐mm o.d.)
  • Three‐way taps
  • Blood pressure transducer
  • Millar transducer
  • Small‐animal bipolar stimulating electrodes (Harvard Apparatus)
  • Stimulator (e.g., Grass S88; Stag Instruments)
  • Surgical swabs
  • Criticath size 7F (110‐cm) cardiac thermodilution catheter (Ohmeda Catheter Products)
  • Polygraph recorder (e.g., Grass) or data acquisition system
  • Cardiac monitor (Gould)

Alternate Protocol 1: Measurement of Pelvic Nerve–Stimulated Bladder Contraction and Cardiovascular Function in the Anesthetized Rat

  Materials
  • 200‐ to 300‐g female caesarean‐derived Sprague‐Dawley rats (Charles River Labs)
  • 25% (w/v) urethane (ethyl carbamate; Sigma; store at room temperature)
  • 0.9% (w/v) NaCl, sterile (store at room temperature)
  • 50 U/ml heparin in sterile 0.9% (w/v) NaCl (store at room temperature, prepare monthly)
  • Test compound solution (e.g., atropine or cromakalim; see recipe)
  • Xylocaine spray (Astra Pharmaceuticals)
  • 60 mg/ml sagatal (pentabarbitone sodium B.P.; Rhone Merieux)
  • Homeothermic blanket control unit equipped with a thermostatic rectal probe (Harvard Apparatus)
  • Pink‐tipped 17‐G single‐use intravenous cannulae (Luer fitting, ref 200/500/030; 1.4‐mm o.d.; 0.6‐mm i.d.; Portex)
  • Three‐way taps
  • Pressure transducers (Ohmeda Catheter Products, P23XL‐1)
  • Tracheal tubing: 1.5‐mm‐i.d., 2.7‐mm‐o.d. polyethylene tubing (ref 800/100/380/100)
  • 4.0 silk ligature
  • Respiration pump (Harvard Apparatus)
  • Small‐animal retractors
  • Dissecting microscope (optional, but recommended)
  • Subminiature bipolar stimulating electrodes (Harvard Apparatus)
  • Stimulator (e.g., Grass S88; Stag Instruments)
  • Polygraph recorder (Grass or equivalent)
  • On‐line data analysis system (e.g., MacLab)

Support Protocol 1: Measurement of Parasympathetic Nerve–Induced Salivary Secretion from the Submandibular Gland of the Dog

  • pp100 cannula (coded 800/100/280/100; 0.86‐mm i.d., 1.52‐mm o.d.)
  • Pressure transducer
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Figures

Videos

Literature Cited

Literature Cited
   Creed, K.E. and Tulloch, A.G.S. 1978. The effect of pelvic nerve stimulation and some drugs on the urethra and bladder of the dog. Br. J. Urol. 50:398‐405.
   Diederichs, W., Sroka, J., and Graff, J. 1992. Comparison of Bay K8644, nitrendipine and atropine on spontaneous and pelvic nerve‐induced bladder contractions on rat bladder in vivo. Urol. Res. 20:49‐53.
   Edwards, G. and Weston, A.H. 1993. The pharmacology of ATP‐sensitive potassium channels. Annu. Rev. Pharmacol. Toxicol. 33:597‐637.
   Langley, J.N. and Anderson, H.K. 1895. The innervation of the pelvic and adjoining viscera. Part II. The bladder. J. Physiol. (Lond.) 19:71‐84.
   Lung, M.A. 1990. Variations in blood flow on mandibular glandular secretion to autonomic nervous stimulations in anesthetized dogs. J. Physiol. (Lond.) 431:479‐493.
   Tiseo, P.J. and Yaksh, T.L. 1990. The spinal pharmacology of urinary function: Studies on the urinary continence of the unanesthetized rat. In Neurobiology of Incontinence (Ciba Foundation Symposium 151) pp. 91‐109. John Wiley & Sons, Chichester, England.
   Ursillo, R.C. and Clark, B.B. 1956. The action of atropine on the urinary bladder of the dog and on the isolated nerve‐bladder strip preparation of the rabbit. J. Pharmacol. Exp. Ther. 118:338‐347.
   Yu, J.‐H. 1992. Effects of chronic clonidine administration on parasympathetic‐evoked rat saliva. Life Sci. 51:1493‐1499.
Key References
   Diederichs et al., 1992. See above.
  First description of in vivo pelvic nerve–stimulated bladder contraction in the rat.
   Lung, 1990. See above.
  First description of in vivo nerve‐stimulated salivation in the dog.
   Ursillo and Clark, 1956. See above.
  Describes recording of bladder contraction in the dog following stimulation of the pelvic nerve.
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