Bladder Function In Rats Research Articles

Effects of Ethanol on in Vivo Cystometry and in Vitro Whole Bladder Contractility in the Rat

Purpose It is known that acute ethanol intoxication can produce urinary retention in patients with benign prostatic hyperplasia. We evaluated the effects of ethanol on rat bladder function in vivo and in vitro. Materials and Methods Infusion cystometry was performed under urethane anesthesia with or without intravenous injection of ethanol. Voided volume, maximum voiding pressure, residual urine, bladder capacity, the pressure at which micturition was induced and voiding efficacy were compared. Subsequently, the in vitro whole bladder pressure generated by field stimulation, bethanechol, adenosine triphosphate and KCl in the presence of ethanol 0 to 5.0 percent was investigated. Results Intravenous administration of ethanol changed the in vivo cystometrogram. Bladder capacity and residual urine volume were significantly increased, and voiding pressure was decreased. Contractility of the isolated whole bladder to various kinds of stimulation in vitro was suppressed by ethanol in a dose-dependent manner. Washing the bladder and incubating it in normal Krebs' solution following exposure to 5 percent ethanol restored detrusor contractility. Conclusion Ethanol significantly impairs detrusor contractility in the rat in vivo and in vitro.

Changes in rat bladder function following exposure to pain and water stimuli.

Changes in rat bladder function following the exposure to physical stress were studied in vitro. Rats were divided into two stress groups and two control groups and maintained for 6 months under specific conditions. The stress groups, consisting of animals subjected to water or pain stress and control groups were kept in cages floored with wooden chips or wire net. The body weight of the stressed groups was significantly lower than that of the controls. Gastric ulcer occurred in none of the groups. The detrusor response of the water group to acetylcholine was significantly greater than that of the two control groups. In the pain group, the contractile response was induced by norepinephrine. In the other three groups, however, norepinephrine evoked a relaxation of muscle strips. The contractile response of the bladder to both serotonin (5-hydroxytryptamine) and ATP (adenosine 5'-triphosphate) did not differ between the four groups.

P-534 - Effect of various drugs on bladder function in rats.

P-534 - Effect of various drugs on bladder function in rats.

The Influence of Acute Overdistension on Rat Bladder Function and DNA Synthesis

Prolonged micturition problems are often encountered after long-term bladder overdistension caused by urinary retention. In animal studies, damage to the bladder wall innervation has been found following overdistension. Experimentally, acute overdistension has also been implicated in the pathogenesis of the response to partial outlet obstruction. In the present study we investigated the influence of overdistension on micturition volume and frequency, on in vitro bladder function using the whole bladder model and on 3H-thymidine uptake, localization and DNA synthesis.Overdistension was induced for 3 hours by forced diuresis and balloon obstruction. Another group of rats was catheterized for 3 hours but received no diuretic, nor was the balloon inflated. An additional group of controls was neither anesthetized nor catheterized. Overdistension caused a gradual increase in bladder mass which was maximal at 7 days. During the first 24 hours following overdistension, the frequency of micturition decreased, but normalized thereafter. A progressive decrease in the response to field stimulation was noted between 16 hours and 7 days following overdistension and remained at this level until 21 days. There were, however, no significant differences in the responses to carbachol, ATP and KCl. There was a 30% reduction in the ability of field stimulation to empty the bladder 16 hours after overdistension, but no impairment of the emptying ability of carbachol. Overdistension was followed by a significant increase in 3H-thymidine uptake, which was maximal at 2 days. 3H-thymidine labelling increased rapidly after overdistension and was maximal within 16 hours in the urothelium. In smooth muscle, connective tissue and lamina propria, maximal labelling occurred at 2 days. Catheterization alone caused a mild distension which was associated with a small, but statistically significant, increase in 3H-thymidine incorporation into DNA within 16 hours. The labelling was located primarily in the urothelium.Overdistension causes a proliferative reaction within the bladder wall. Its initial effects occur within the urothelium, and the later involvement of the subendothelial smooth muscle and connective tissue is directly proportional to the degree of bladder distension. Three weeks following overdistension, the bladder’s functional state was not completely recovered, although the urinary bladder was found to have a good capacity to adapt and compensate for the stress-induced changes caused by overdistension. It is, therefore, clear that overdistension may have long-lasting effects on the bladder.

Urinary Bladder Function in Rats with Hereditary Diabetes Insipidus; A Cystometrical and in Vitro Evaluation

Bladder function was investigated in female rats with hereditary diabetes insipidus (DI) and in healthy controls, in vivo by means of recordings of micturition pattern and cystometry, and in vitro in organ bath experiments. Rats with DI exhibited bladder hypertrophy, the weight of the bladder in these rats being two times that of controls. Recordings of micturition pattern showed that DI-rats had an increased 24hour diuresis and micturition volume, and decreased micturition interval in comparison with controls. Cystometry recordings revealed increased bladder capacity and micturition volume in DI-rats. However, in these rats basal bladder pressure and threshold pressure were lower than in controls. No significant changes in micturition pressure or bladder compliance were observed, and none of the rats had residual urine. In organ bath studies, a lower maximal response to electrical field stimulation was obtained in bladder strips from DI-rats, than in the control strips, when expressed relative to the response elicited by K+-solution. When activated by field stimulation, the DI-bladder strips and the control strips had similar sensitivity to muscarinic receptor blockade with scopolamine at all stimulation frequencies. The sensitivity to carbachol was similar in the two groups. The results suggest that the increased functional demands of DI on the detrusor do not result in major changes pre- or postjunctionally. Further, several of the previously reported urinary bladder changes observed in rats with diabetes mellitus (DM) are similar to those now reported in rats with DI, emphasizing the importance of an increased diuresis per se for the development of alterations in bladder function. However, in contrast to the findings in DM rats, the sensitivity to electrical stimulation of nerves during blockade of muscarinic receptors was similar in DI-rats and their controls. This supports our previous suggestion that the increased resistance to muscarinic receptor blockade of the bladder in DM-rats at low stimulation frequencies is induced by the disease (diabetes mellitus) as such and not by the increased diuresis.

The Influence of Ovariectomy and Estradiol Replacement on Urinary Bladder Function in Rats

Female Fischer 344 rats were ovariectomized or sham operated and treated with oil or estradiol cypionate (100mg./100 gm./month) for two or four months. Rats were then placed in metabolism cages for measurement of micturition characteristics, and bladders were removed for bladder strip studies. Ovariectomy had no effects on micturition characteristics. However, estradiol treatment of ovariectomized rats caused significant increases in water consumption and urine excretion, and in mean and maximal micturition volumes compared to both ovariectomized and sham-operated rats. These effects were more pronounced at four months. Estradiol treatment also caused significant increases in bladder body mass, while ovariectomy was without effect. Two months after ovariectomy and/or estradiol treatment, there were no differences in contractile responses of bladder body or base strips to contractile agents when compared to shams. However, after four months, ovariectomy caused significant decreases in contractile responsiveness to nerve stimulation, ATP, carbachol, and KCl compared to sham-operated rats. Estradiol treatment caused increased responsiveness to nerve stimulation, ATP, carbachol, and KCl compared to ovariectomized rats, and to carbachol compared to sham operated rats. Possible causes for the effects of ovariectomy on bladder contractility include decreases in calcium influx. Although estradiol reversed the effects of ovariectomy on bladder function, in addition we observed some indirect effects which were probably the result of estradiol-induced polyuria and increases in bladder mass.

On the Reversibility of Functional Bladder Changes Induced by Infra Vesical Outflow Obstruction in the Rat

Rats were subjected to infravesical outflow obstruction for six weeks. The bladder function was followed by cystometrical and in vitro investigations and by recordings of micturition pattern before and after removal of the obstruction.Cystometrical investigations showed that outflow obstruction for six weeks induced a bladder instability. Further, in the presence of obstruction the micturition pressure was large as was the bladder capacity and the rats had residual urine. After removal of the obstruction the bladder function rapidly normalized. The bladder instability disappeared within one week, bladder capacity decreased as did the micturition pressure. Moreover, only a minor amount of residual urine was present post-obstruction.In vitro investigation showed that the response to carbachol and to electrical stimulation was similar in normal and obstructed bladders. However, after removal of the obstruction a supersensitivity to carbachol as well as to electrical stimulation had developed. Obstructed bladders showed a markedly decreased response to substance P. The sensitivity to substance P was rapidly enhanced post-obstruction and after four days the response was restored to the control level.The present study shows that the bladder function in rats with infravesical outflow obstruction rapidly normalized after removal of the obstruction. The disappearance of the bladder instability despite the developed supersensitivity to muscarinic receptor stimulation supports the opinion that the bladder instability is not of muscarinic origin. (J. Urol., 143:1026-1031, 1990)

In vivo urinary bladder function in rats following prolonged diabetic and non‐diabetic diuresis

AbstractChanges in urinary bladder function are present in animal models of diabetes mellitus. In vivo cystometry in diabetic rats shows a bladder with increased capacity and a raised threshold for initiation of the micturition reflex. At sacrifice, diabetic rats have bladder hypertrophy, resulting in approximately a doubling of the bladder weight.This study was designed to characterize the effects of diabetes on micturition in the streptozotocin‐diabetic rat. For comparative purposes, two different control groups were examined: 1) age‐matched control rats and 2) age‐matched rats which were given 5% sucrose to drink. Sucrose‐fed rats consumed large volumes of fluid resulting in diuresis and bladder hypertrophy.Fluid consumption and excretion were significantly increased in diabetic and sucrose‐drinking rats. In addition, the diabetic rats both drank and excreted more than the sucrose‐drinking rats. Control rats had twice as many micturitions during the dark cycle than during the light cycle, but the volume micturition during the dark cycle was less than one‐half the volume per micturition during the light cycle. Sucrose drinking rats had the same number of micturitions as control rats during the light cycle. but the volumes per micturition were significantly increased. During the dark cycle, the number of micturitions increased four‐fold and the volume per micturition was significantly increased compared to controls. The diabetic rats, in contrast to the two control groups, had a significant increase in the number of micturitions during the light and dark cycles. Similar to the sucrose drinking rats, the volumes excreted per micturition were significantly greater than the normal controls. The data are discussed with regard to the effects of prolonged diuresis on bladder function and hypertrophy.

Effects of m-chlorophenylpiperazine on penile and bladder function in rats.

The effects of m-chlorophenylpiperazine (MCPP), a serotonin agonist, on spontaneous and evoked neural firing in nerves supplying the penis and bladder were examined in the urethan-anesthetized rat. MCPP (0.1-10 mg/kg iv) elicited, after a 2- to 4-min delay, an increase in spontaneous firing in cavernous nerves but no detectable firing in bladder nerves. The cavernous nerve firing was accompanied by an increase in intracavernous pressure and a depression of rhythmic bladder activity. Administration of ganglionic-blocking agents or transection of peripheral nerves revealed that the cavernous nerve discharge was mediated by activation of pre-ganglionic cholinergic pathways in the pelvic nerve. The effects of MCPP were noted in intact as well as in acute and chronic spinal rats and were prevented by the administration of the serotonin (5-HT) antagonist, metergoline (3 mg/kg im). These data indicate that pharmacological activation of 5-HT receptors, possibly of the 5-HT1B subtype, can facilitate the sacral preganglionic outflow to the penis and inhibit bladder activity.

Bladder Function in Rats with Short- and Long-Term Diabetes; Effects of Age and Muscarinic Blockade

The development of alterations in urinary bladder function was studied in rats during six months of streptozotocin-induced diabetes. The results were compared with those obtained in age-matched controls. The bladders from the control rats developed with increasing age an increased micturition volume, a decreased micturition interval, and increased bladder compliance and capacity despite an unaltered bladder weight and unaltered passive and active length-tension relations. The effects of muscarinic blockade were somewhat more pronounced in the older control rats.Following streptozotocin 24 hour diuresis increased rapidly to stabilize within two weeks at a level 15 times higher than the original. This was accomplished initially by an increase in the micturition frequency and then gradually by an increased micturition volume. After six weeks bladder weight had increased more than twofold and did not increase further with time. Despite this both micturition volume and bladder capacity increased from six weeks to six months of diabetes. The diabetic bladders had at low frequencies of stimulation a higher resistance to scopolamine than their age-matched controls. At higher frequencies the resistance to muscarinic blockade showed a similar decrease with age as for the controls. The more pronounced decrease in micturition pressure following atropine treatment in six weeks diabetic rats thus suggests an increased excitation frequency during micturition. No supersensitivity to carbachol was found even after six months of diabetes.

Effects of Pinacidil and Cromakalim (BRL 34915) On Bladder Function in Rats with Detrusor Instability

Normal rats as well as rats with bladder hypertrophy secondary to outflow obstruction were investigated cystometrically before and after administration of the potassium channel openers pinacidil or cromakalim one mg./kg. orally.In normal rats cromakalim decreased micturition pressure by 15 ± 6%. A diminished micturition pressure was also seen after pinacidil (by 18 ± 8%) but this did not achieve statistical significance. Further, no clear-cut effects on bladder capacity, residual volume, basal bladder pressure, threshold pressure, bladder compliance or on bladder wall tension were seen in this group of rats neither in the presence of pinacidil nor cromakalim.Rats with bladder hypertrophy exhibited a significant bladder instability during cystometrical investigations. The mean amplitude of the spontaneous bladder contractions exceeded 20cm. H20 prior to micturition. Administration of pinacidil and cromakalim decreased the spontaneous contractions to 26 ± 12% and 22 ± 7%, respectively, of that seen in the absence of the drugs. Furthermore, pinacidil decreased micturition pressure by 61 ± 12%. Also cromakalim decreased micturition pressure (by 27 ± 13%) but this effect did not achieve statistical significance. After both pinacidil and cromakalim these rats tended to develop residual urine. In accordance with the results in normal rats pinacidil and cromakalim showed no effects on bladder capacity, basal bladder pressure, threshold pressure, bladder compliance or on bladder wall tension in rats with bladder hypertrophy.The findings of an almost complete disappearance of spontaneous bladder contractions in rats with bladder instability and a remaining voiding ability after administration of pinacidil or cromakalim suggest that potassium channel openers may be a therapeutic alternative in the treatment of bladder instability associated with outflow obstruction.

Effects of neonatal capsaicin treatment and streptozotocin-induced diabetes on urinary bladder function in rats

A significant increase in the size and weight of the urinary bladder was observed 2 weeks after streptozotocin treatment and 2 months after neonatal capsaicin treatment. Both treatments induced a significant increase in the level of [ 3H]quinuclidinyl benzilate binding to muscarinic cholinergic receptors in the urinary bladder membranes. However, contractile responses of urinary bladder muscle strips to carbachol (0.3–20 μM) were not significantly affected by either treatment. On the other hand, neonatal capsaicin treatment, but not streptozotocin treatment, significantly enhanced contractile responses of bladder strips to electric field stimulation.

Cystometrical and in Vitro Evaluation of Urinary Bladder Function in Rats with Streptozotocin-Induced Diabetes

Micturition pattern and cystometric characteristics were determined in control rats, and in rats with streptozotocin-induced diabetes (six weeks duration). The diabetic rats had an increased frequency of micturition, an increased micturition volume, and an increased 24 hr. urinary output. The cystometry showed that the diabetic bladders had an increased compliance and a higher threshold volume for initiating a micturition reflex. No spontaneous rhythmic contractions were seen during the filling phase, and no residual urine could be detected. While micturition pressure increased, the micturition time was virtually unaltered. In vitro a right-ward shift for passive and active length-tension relations was noted. The observed changes in cystometric characteristics and length-tension relations might probably be explained on the basis of adaptive changes to the increased diuresis involving both sensory and motor control of the urinary bladder