Rodent models for urodynamic investigation

Rodents, most commonly rats, mice, and guinea pigs are widely used to investigate urinary storage and voiding functions, both in normal animals and in models of disease. An often used methodology is cystometry. Micturitions in rodents and humans differ significantly and this must be considered when cystometry is used to interpret voiding in rodent models. Cystometry in humans requires active participation of the investigated patient (subject), and this can for obvious reasons not be achieved in the animals. Cystometric parameters in rodents are often poorly defined and do not correspond to those used in humans. This means that it is important that the terminology used for description of what is measured should be defined, and that the specific terminology used in human cystometry should be avoided. Available disease models in rodents have limited translational value, but despite many limitations, rodent cystometry may give important information on bladder physiology and pharmacology. The present review discusses the principles of urodynamics in rodents, techniques, and terminology, as well as some commonly used disease models, and their translational value. Neurourol. Urodynam. Neurourol. Urodynam. 30:636–646, 2011. © 2011 Wiley‐Liss, Inc.

[1]  G. McMurray,et al.  Animal models in urological disease and sexual dysfunction , 2006, British journal of pharmacology.

[2]  Y. Park,et al.  Changes of urinary nerve growth factor and prostaglandins in male patients with overactive bladder symptom , 2005, International journal of urology : official journal of the Japanese Urological Association.

[3]  J. Wrathall,et al.  Altered glutamate receptor function during recovery of bladder detrusor-external urethral sphincter coordination in a rat model of spinal cord injury. , 2002, The Journal of pharmacology and experimental therapeutics.

[4]  J. Brioni,et al.  Characterization of a novel ATP‐sensitive K+ channel opener, A‐251179, on urinary bladder relaxation and cystometric parameters , 2007, British journal of pharmacology.

[5]  D. Newgreen,et al.  Detrusor responses to prostaglandin E2 and bladder outlet obstruction in wild-type and Ep1 receptor knockout mice. , 2004, The Journal of urology.

[6]  D. Newgreen,et al.  Bladder overactivity in mice after 1 week of outlet obstruction. Mainly afferent dysfunction? , 2003, The Journal of urology.

[7]  M. P. Freire,et al.  Urine is necessary to provoke bladder inflammation in protamine sulfate induced urothelial injury. , 2008, The Journal of urology.

[8]  G. Kuchel,et al.  Continuous uroflow cystometry in the urethane‐anesthetized mouse , 2010, Neurourology and urodynamics.

[9]  T. Streng,et al.  Transmitters contributing to the voiding contraction in female rats , 2004, BJU international.

[10]  T. Streng,et al.  The role of the rhabdosphincter in female rat voiding , 2004, BJU international.

[11]  A. Brading,et al.  Electrical and mechanical responses of guinea‐pig bladder muscle to nerve stimulation , 1989, British journal of pharmacology.

[12]  M. Damaser,et al.  Effects of anesthesia on cystometry and leak point pressure of the female rat. , 2001, Life sciences.

[13]  T. Streng,et al.  Similarities and differences in female and male rat voiding , 2002, Neurourology and urodynamics.

[14]  T. Lue,et al.  An animal model to study lower urinary tract symptoms and erectile dysfunction: the hyperlipidaemic rat , 2007, BJU international.

[15]  M. Takeda,et al.  Sex-related differences in activity of lower urinary tract in response to intravesical acid irritation in decerebrate unanesthetized mice. , 2008, American journal of physiology. Regulatory, integrative and comparative physiology.

[16]  G. Lin,et al.  Adipose derived stem cells ameliorate hyperlipidemia associated detrusor overactivity in a rat model. , 2010, The Journal of urology.

[17]  Role of the Forebrain in Bladder Overactivity Following Cerebral Infarction in the Rat , 2000, Experimental Neurology.

[18]  L. Jasmin,et al.  Assessment of lower urinary tract functional deficit in rats with contusive spinal cord injury. , 1998, Journal of neurotrauma.

[19]  W. D. de Groat,et al.  Urethral dysfunction in diabetic rats. , 2004, The Journal of urology.

[20]  K. Andersson,et al.  Role of dopamine D1 and D2 receptors in the micturition reflex in conscious rats , 2001, Neurourology and urodynamics.

[21]  K. Andersson,et al.  Urodynamic effects of intravesical resiniferatoxin and capsaicin in conscious rats with and without outflow obstruction. , 1995, The Journal of urology.

[22]  Naoki Yoshimura,et al.  Changes in afferent activity after spinal cord injury , 2010, Neurourology and urodynamics.

[23]  M. Kakiuchi,et al.  Effects of various drugs on bladder function in conscious rats. , 1989, Japanese journal of pharmacology.

[24]  K. Thor,et al.  Animal models and their use in understanding lower urinary tract dysfunction , 2010, Neurourology and urodynamics.

[25]  M. Kitahara,et al.  Voiding dysfunction and Parkinson's disease: urodynamic abnormalities and urinary symptoms. , 2000, The Journal of urology.

[26]  G. Somogyi,et al.  Comparison of cystometric methods in female rats , 2008, Neurourology and urodynamics.

[27]  Weixin Zhao,et al.  Impaired bladder function in aging male rats. , 2010, The Journal of urology.

[28]  M. Siroky,et al.  Alteration of urothelial‐mediated tone in the ischemic bladder: Role of eicosanoids , 2004, Neurourology and urodynamics.

[29]  J. Williams,et al.  Contractile responses of smooth muscle strips from rat and guinea-pig urinary bladder to transmural stimulation: effects of atropine and alpha,beta-methylene ATP. , 1990, British journal of pharmacology.

[30]  H. Son,et al.  New unstable bladder model in hypercholesterolemia rats. , 2007, Urology.

[31]  P. Hellstrand,et al.  Effect of melatonin on age associated changes in Guinea pig bladder function. , 2007, The Journal of urology.

[32]  F. Daneshgari,et al.  Animal models of diabetic uropathy. , 2009, The Journal of urology.

[33]  W. Steers,et al.  Spinal and peripheral mechanisms contributing to hyperactive voiding in spontaneously hypertensive rats. , 1998, The American journal of physiology.

[34]  G. Gabella,et al.  Intramural neurones appear in the urinary bladder wall following excision of the pelvic ganglion in the rat. , 1995, Neuroreport.

[35]  Y. Kojima,et al.  Altered distribution of interstitial cells in the guinea pig bladder following bladder outlet obstruction. , 2008, Neurourology and urodynamics.

[36]  Dopaminergic mechanisms underlying bladder hyperactivity in rats with a unilateral 6‐hydroxydopamine (6‐OHDA) lesion of the nigrostriatal pathway , 2003, British journal of pharmacology.

[37]  W. D. de Groat,et al.  Intravesical protamine sulfate and potassium chloride as a model for bladder hyperactivity. , 2003, Urology.

[38]  C. Bishop,et al.  A Mutation in the Inner Mitochondrial Membrane Peptidase 2-Like Gene (Immp2l) Affects Mitochondrial Function and Impairs Fertility in Mice1 , 2008, Biology of reproduction.

[39]  J. Downie,et al.  Effect of anesthetics on reflex micturition in the chronic cannula‐implanted rat , 2000, Neurourology and urodynamics.

[40]  N. Yoshimura,et al.  Long-term effects of diabetes mellitus on voiding function in a new model of type 2 diabetes mellitus, the Spontaneously Diabetic Torii (SDT) rat. , 2009, Biomedical research.

[41]  W. D. de Groat,et al.  Influence of anesthesia on bladder hyperactivity induced by middle cerebral artery occlusion in the rat. , 1997, The American journal of physiology.

[42]  A. Arner,et al.  Urinary bladder contraction and relaxation: physiology and pathophysiology. , 2004, Physiological reviews.

[43]  T. Streng,et al.  Phasic non‐micturition contractions in the bladder of the anaesthetized and awake rat , 2006, BJU international.

[44]  A. Leonardi,et al.  Influence of pump compliance (peristaltic vs. infusion) on urodynamic measurement during cystometry in conscious rats. , 2001, Journal of pharmacological and toxicological methods.

[45]  C. Fowler Update on the neurology of Parkinson's disease , 2007, Neurourology and urodynamics.

[46]  J. J. de la Rosette,et al.  Age and bladder outlet obstruction are independently associated with detrusor overactivity in patients with benign prostatic hyperplasia. , 2008, European urology.

[47]  M. Damaser,et al.  Effects of vaginal distension on urethral anatomy and function , 2002, BJU international.

[48]  A. Ziomber,et al.  Urodynamic effects of the bladder C-fiber afferent activity modulation in chronic model of overactive bladder in rats. , 2009, Journal of physiology and pharmacology : an official journal of the Polish Physiological Society.

[49]  A. Brading,et al.  Contractile responses of smooth muscle strips from rat and guinea‐pig urinary bladder to transmural stimulation: effects of atropine and α,β‐methylene ATP , 1990 .

[50]  Magnus Fall,et al.  The standardisation of terminology in lower urinary tract function: report from the standardisation sub-committee of the International Continence Society. , 2003, Urology.

[51]  D. Brooks,et al.  Influence of genetic background and gender on bladder function in the mouse , 2008, Autonomic Neuroscience.

[52]  D. Andersson,et al.  Distribution and function of the hydrogen sulfide-sensitive TRPA1 ion channel in rat urinary bladder. , 2008, European urology.

[53]  W. Bushman,et al.  Acute acrolein‐induced cystitis in mice , 2007, BJU international.

[54]  M. Namiki,et al.  Role of cyclooxygenase-2 in the development of bladder overactivity after cerebral infarction in the rat. , 2005, The Journal of urology.

[55]  S. Biers,et al.  The functional effects of a c‐kit tyrosine inhibitor on guinea‐pig and human detrusor , 2006, BJU international.

[56]  H. Akino,et al.  Role of glutamate receptors in the development and maintenance of bladder overactivity after cerebral infarction in the rat. , 2004, The Journal of urology.

[57]  M. Damaser,et al.  Voiding function in obese and type 2 diabetic female rats. , 2010, American journal of physiology. Renal physiology.

[58]  T. Streng,et al.  Simultaneous registration of intraabdominal and intravesical pressures during cystometry in conscious rats—Effects of bladder outlet obstruction and intravesical PGE2 , 2008, Neurourology and urodynamics.

[59]  T. Mitsui,et al.  GABAergic mechanism mediated via D1 receptors in the rat periaqueductal gray participates in the micturition reflex: an in vivo microdialysis study , 2008, The European journal of neuroscience.

[60]  K. Kihara,et al.  Effects of anaesthesia on the nitrergic pathway during the micturition reflex in rats , 2007, BJU international.

[61]  J. Wrathall,et al.  Coordination of the Bladder Detrusor and the External Urethral Sphincter in a Rat Model of Spinal Cord Injury: Effect of Injury Severity , 2001, The Journal of Neuroscience.

[62]  T. Doi,et al.  Effects of TAK‐802, a novel acetylcholinesterase inhibitor, and tamsulosin, an α1‐adrenoceptor antagonist, and their synergistic effects on the urodynamic characteristics in a guinea‐pig model of functional bladder outlet obstruction , 2005, BJU international.

[63]  M. Sacks,et al.  Diabetes-induced alternations in biomechanical properties of urinary bladder wall in rats. , 2009, Urology.

[64]  K. Andersson,et al.  Stimulation of skin menthol receptors stimulates detrusor activity in conscious rats , 2010, Neurourology and urodynamics.

[65]  R. Krane,et al.  Atherosclerosis-induced chronic ischemia causes bladder fibrosis and non-compliance in the rabbit. , 1999, The Journal of urology.

[66]  C. Parsons,et al.  Bladder injury model induced in rats by exposure to protamine sulfate followed by bacterial endotoxin. , 1996, The Journal of urology.

[67]  J. Roppolo,et al.  Alteration by urethane of glutamatergic control of micturition. , 1994, European journal of pharmacology.

[68]  Weixin Zhao,et al.  Evaluation of two techniques of partial urethral obstruction in the male rat model of bladder outlet obstruction. , 2005, Urology.

[69]  T. Manabe,et al.  Cystometric findings in mice lacking muscarinic M2 or M3 receptors. , 2004, The Journal of urology.

[70]  M. Kakiuchi,et al.  Effects of various drugs on bladder function in conscious restrained-denervated rats placed in a restraining cage and produced by transection of the hypogastric nerve. , 1990, Japanese journal of pharmacology.

[71]  R. Pandita,et al.  Oxytocin-induced stimulation and inhibition of bladder activity in normal, conscious rats—Influence of nitric oxide synthase inhibition , 1998, Neuroscience.

[72]  K. Trott,et al.  Post-irradiation bladder dysfunction: development of a rat model , 2004, Urological Research.

[73]  Urethral afferent nerve activity affects the micturition reflex; implication for the relationship between stress incontinence and detrusor instability. , 1999, The Journal of urology.

[74]  M. Vizzard,et al.  Expression of corticotropin-releasing factor and CRF receptors in micturition pathways after cyclophosphamide-induced cystitis. , 2006, American journal of physiology. Regulatory, integrative and comparative physiology.

[75]  G. Christ,et al.  Spinal effects of the fesoterodine metabolite 5-hydroxymethyl tolterodine and/or doxazosin in rats with or without partial urethral obstruction. , 2010, The Journal of urology.

[76]  C. Maggi,et al.  Effect of urethane anesthesia on the micturition reflex in capsaicin-treated rats. , 1990, Journal of the autonomic nervous system.

[77]  C. Gratzke,et al.  Urodynamic evaluation of fesoterodine metabolite, doxazosin and their combination in a rat model of partial urethral obstruction , 2009, BJU international.

[78]  M. Namiki,et al.  Contribution of cerebral nitric oxide to bladder overactivity after cerebral infarction in rats. , 2002, The Journal of urology.

[79]  D. Clarke,et al.  Effect of cyclooxygenase inhibitors on the micturition reflex in rats: correlation with inhibition of cyclooxygenase isozymes , 2006, BJU international.

[80]  Weixin Zhao,et al.  Alterations in bladder function associated with urothelial defects in uroplakin II and IIIa knockout mice , 2009, Neurourology and urodynamics.

[81]  R. Pandita,et al.  Cystometric evaluation of bladder function in non-anesthetized mice with and without bladder outlet obstruction. , 2000, The Journal of urology.

[82]  T. Yaksh,et al.  Micturition in rats: a chronic model for study of bladder function and effect of anesthetics. , 1986, The American journal of physiology.

[83]  H. Higashiyama,et al.  A new method for producing urinary bladder hyperactivity using a non-invasive transient intravesical infusion of acetic acid in conscious rats. , 2008, Journal of pharmacological and toxicological methods.

[84]  T. Streng,et al.  Possible action of the proximal rhabdosphincter muscle in micturition of the adult male rat , 2001, Neurourology and urodynamics.

[85]  W. D. de Groat,et al.  GABA receptor activation in the lumbosacral spinal cord decreases detrusor overactivity in spinal cord injured rats. , 2008, The Journal of urology.

[86]  K. Andersson,et al.  Cystometrical evaluation of bladder instability in rats with infravesical outflow obstruction. , 1987, The Journal of urology.

[87]  C. Fry,et al.  Experimental models to study the physiology, pathophysiology, and pharmacology of the lower urinary tract. , 2004, Journal of pharmacological and toxicological methods.

[88]  A. Aszódi,et al.  Functional characteristics of urinary tract smooth muscles in mice lacking cGMP protein kinase type I. , 2000, American journal of physiology. Regulatory, integrative and comparative physiology.

[89]  Y. Park,et al.  Nerve growth factor and prostaglandins in the urine of female patients with overactive bladder. , 2006, The Journal of urology.

[90]  A. Wein Bladder injection of "naked" hSlo/pcDNA3 ameliorates detrusor hyperactivity in obstructed rats in vivo. , 2003, The Journal of urology.

[91]  M. Saito,et al.  Bladder dysfunction after acute urinary retention in rats. , 2001, The Journal of urology.

[92]  R. Pandita,et al.  Intravesical adenosine triphosphate stimulates the micturition reflex in awake, freely moving rats. , 2002, The Journal of urology.

[93]  L. Havton,et al.  Differential effects of urethane and isoflurane on external urethral sphincter electromyography and cystometry in rats. , 2008, American journal of physiology. Renal physiology.

[94]  T. Lue,et al.  Long-term effect of ovariectomy and simulated birth trauma on the lower urinary tract of female rats. , 2002, The Journal of urology.

[95]  S. Palea,et al.  Pharmacological and urodynamic changes in rat urinary bladder function after multiple pregnancies , 1999, BJU international.

[96]  C. Bishop,et al.  Bladder dysfunction in a new mutant mouse model with increased superoxide--lack of nitric oxide? , 2010, The Journal of urology.

[97]  L. Rodríguez,et al.  New objective measures to quantify stress urinary incontinence in a novel durable animal model of intrinsic sphincter deficiency. , 2005, American journal of physiology. Regulatory, integrative and comparative physiology.

[98]  A. Phillips,et al.  Rodent models of nephropathy associated with type II diabetes. , 1999, Journal of nephrology.

[99]  K. Andersson,et al.  Development of bladder dysfunction in a rat model of dopaminergic brain lesion , 2011, Neurourology and urodynamics.

[100]  K. Andersson,et al.  Prostaglandin E2-induced bladder hyperactivity in normal, conscious rats: involvement of tachykinins? , 1995, The Journal of urology.

[101]  J. Roppolo,et al.  Electrophysiological analysis of the ascending and descending components of the micturition reflex pathway in the rat , 1991, Brain Research.

[102]  H. Bruschini,et al.  Voiding dysfunction in patients with Parkinson's disease: Impact of neurological impairment and clinical parameters , 2009, Neurourology and urodynamics.

[103]  R. Pehrson,et al.  Effects of tramadol on rat detrusor overactivity induced by experimental cerebral infarction. , 2003, European Urology.

[104]  C. Maggi,et al.  Analysis of factors involved in determining urinary bladder voiding cycle in urethan-anesthetized rats. , 1986, The American journal of physiology.

[105]  Long-Hu Jin,et al.  Selection of a control rat for conscious spontaneous hypertensive rats in studies of detrusor overactivity on the basis of measurement of intra‐abdominal pressures , 2010, Neurourology and urodynamics.

[106]  W. Steers,et al.  Alterations in voiding frequency and cystometry in the clomipramine induced model of endogenous depression and reversal with fluoxetine. , 2003, The Journal of urology.