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

Abstract

Neuronal control of the lower urinary tract is a highly complex, integrated process, involving sympathetic, parasympathetic, and sensory neuronal pathways for normal coordinated function. Dysfunction of this integrated mechanism is associated with disorders of the lower urinary tract, most typically urinary incontinence. This unit describes model systems for the measurement of the effects of drugs on bladder function.The first protocol provides a model for measuring the increase in bladder pressure in anesthetized dogs evoked by pelvic nerve stimulation, and for evaluating the effects of pharmacological agents on this response (see Basic Protocol). The same procedure is also described for anesthetized rats (see Alternate Protocol). This model is primarily used to investigate the effects of agents that modify the efferent parasympathetic neuronal drive to the bladder, or that directly relax the smooth muscle of the bladder wall. This preparation is suitable for simultaneous measurement of heart rate, blood pressure, cardiac output, and regional blood flow. Nerve-stimulated salivary secretion can also be measured (see Support Protocol). This is particularly relevant when investigating agents that modulate parasympathetic drive (such as muscarinic antagonists), as it allows for the measurement of relative selectivity on bladder function over the salivary gland. This unit is part of a series describing in vivo models for the assessment of pharmacological agents on lower urinary tract function. UNIT 5.10 describes both anesthetized and conscious animal models of prostate function, while this unit and UNIT 5.12 are primarily for the assessment of bladder function. The anesthetized animal models in this unit offer the potential to measure additional selectivity parameters such as blood pressure, heart rate, and salivation, and to investigate multiple compound concentrations in the same animal. UNIT 5.12 describes a conscious rat model that is arguably closer to normal physiology. However, this model does not permit measurement of additional parameters, and it is more resource intensive as compounds have to be investigated as single doses in any one day. It is important to note that while the models described here and in UNITS 5.10 & 5.12 assess potential pharmacological effects at the level of the lower urinary tract, they are not models of disease state or progression. Caveats associated with the use of rodent and canine models of incontinence include anatomical, physiological, and behavioral differences between the rodent, canine, and human genitourinary systems. For example, rodents and canines (unlike humans) use urination for territorial marking. NOTE: All protocols using live animals must first be reviewed and approved by an Institutional Animal Care and Use Committee (IACUC) or must conform to governmental regulations regarding the care and use of laboratory animals. BASIC PROTOCOL MEASUREMENT OF PELVIC NERVE-STIMULATED BLADDER CONTRACTION AND CARDIOVASCULAR FUNCTION IN THE ANESTHETIZED DOGThis protocol describes...

Megaloneurite, a giant neurite of vasoactive intestinal peptide and nitric oxide synthase in the aged dog and identification by human sacral spinal cord

“…In general, dog is suggested to be suitable animal model for aging research [36,37]. These previous dog model of urogenital dysfunction should be considered with aging study in future [110,111]. In…”