Introduction and Objectives
Different types of animal overactive bladder (OAB) models were described. The cyclophosphamide (CYP)-induced OAB is still the most frequent used model. Therefore CYP-induced morphological changes can trammel the induction of the most similar animal OAB to humans. Hypertonic solutions activate the local efferent activity of bladder capsaicin-sensitive C neurons and as a consequence induce neurogenic inflammation leading to functional impairment of urinary bladder and LUTS (Lower Urinary Tract Symptoms). It suggests that this event may have some relevance in pathogenesis of OAB in which hypertonic urine may diffuse to submucosal layers and activate afferent C-fibres endings. A non-invasive hyperosmolar OAB model was established that is more physiological compared with CYP-induced OAB. In the study the intravesical impact of the hypertonic saline on bladder motor activity was assessed.
Material and Methods
Experiments were performed on 30 female Wistar rats. Cystometry was done after a 1 h recovery period from the surgical procedure under urethane anaesthesia. All animals were randomly divided into four groups: I: control – 308 mOsm/l, II: hypertonic – 1553 mOsm/l, III: hypertonic – 2080 mOsm/l, IV: hypertonic – 3222 mOsm/l. The measurements represent the average of five bladder micturition cycles. The following cystometric parameters were analyzed: basal (BP), threshold (TP), micturition voiding pressure (MVP); intercontraction interval (ICI); compliance; functional bladder capacity (fBC); motility index (MI); detrusor overactivity index (DOI). The Kulick's experiment obtained that 16 h of water deprivation proved sufficient to determine urine concentrating ability of kidneys. Therefore, water deprivation for >16 h was not necessary to perform a meaningful urine concentration test. The concerning urine concentration tests in female rats revealed that mean urine osmolarity was 2080 mOsm/l. Also the lowest and highest value observed for urine osmolarity were 1553 mOsm/l and 3222 mOsm/l, respectively
Intravesical infusion of hypertonic saline induces OAB. The severity of OAB depends on the concentration of saline. All hypertonic infused rats did not exhibit macroscopical signs of bladder inflammation. 1553 mOsm/l saline infusion leads to increase of DOI. During 2080 mOsm/l saline infusion we observed decrease of ICI and fBC. Also increase of BP, DOI and MI. Infusion of 3222 mOsm/l saline induced utmost OAB.
Our results obtained, that hypertonic NaCl solutions within physiological osmolarity range induce concentrated-dependent OAB. The 2080 mOsm/l animal hyperosmolar OAB model closely resembles the physiological micturition reflex and pathophysiology of OAB compared with CYP – induced OAB. This OAB model seems to be the less invasive, what is important for evaluating novel therapeutics to treat the OAB disorder.
© 2009 European Association of Urology. Published by Elsevier Inc. All rights reserved.