Comparison of urinary bladder function in 6 and 24 month male and female rats.

Micturition characteristics, collagen composition, and in vitro urinary bladder strip contractility were examined in young adult (six month) and old (24 month) male and female Fischer 344 rats. Although young female rats consumed significantly less water than young males, there were no differences in volumes of urine excreted. Old females excreted significantly more urine than old males, but there were no differences in volumes of water consumed. Old male rats had similar micturition frequencies during the light and dark cycles, in contrast to females and young males, where the number of micturitions during the dark cycle was significantly greater than those during the light cycle. The mean and maximal micturition volumes were significantly greater in old males compared to young males and old females during both the light and dark cycles. Bladders from female rats weighed significantly less than bladders from males of the same age, and the bladders from young rats weighed less than those of old rats. The protein and collagen concentrations were significantly less in bladder bodies from young females than old females. The amount of collagen resistant to digestion by Pronase, and thus thought to be cross-linked, was significantly greater in bladders from old rats compared to young. No differences between groups were found in the contractile responses of bladder base strips. There were trends for the absolute contractile responses of bladder body strips from old males to field stimulation, carbachol, ATP, and KCl to be larger than the other groups, and for strips from the young females to be smaller. The responses of strips from young females to field stimulation and KCl were significantly less than those of young males or old females, and responses to 10(-3) M ATP were less than those of old females. Responses of strips from old males to 60 mM KCl were significantly greater than those of young males. The differences in contractility could be attributed to the differences in strip mass. It appears, therefore, that urinary bladder function in male and female rats is unaffected by increasing age between 6 and 24 months.     

Effects of age on urinary bladder function in the male rat

In a previous study we investigated the effects of age on the micturition characteristics and bladder function of male Fischer rats ages five to seven, 16 to 18 and 22 to 24 months. The 24 hr. water intake and urine output increases significantly with age; 22 to 24 month rats showed a 39% increase in water intake and a 93% increase in urine output compared to five to seven month rats. The intravesical pressure at micturition is 100% greater in 22 to 24 month and 16 to 18 month rats compared to five to seven month old rats with no age-related change in bladder volume at micturition. In the present study, in vitro bladder capacity did not differ between the three age groups although the average plateau pressure significantly decreased with advancing age. Using the isolated whole bladder model, the contractile response to the autonomic agonists bethanechol, phenylephrine, and isoproterenol did not change significantly with age. Similarly, there were no age-related changes in the response of the bladder to non-autonomic drugs (histamine, oxytocin, serotonin, substance P, and PGF2 alpha) except for PGF2 alpha which produced an age-related increase in the maximum bladder contraction. In summary, while in vivo micturition clearly changes with age, the in vitro contractility of the bladders to autonomic agents did not. Therefore, age related differences in micturition would be related primarily to the changes in neuronal innervation and central control of micturition rather than alterations in the contractility of the bladder. In addition, these studies show the importance of correlating in vivo bladder function (micturition frequency and volume, cystometry and urodynamics) with in vitro contractile and functional studies.     

Collagen and bladder function in streptozotocin-diabetic rats: effects of insulin and aminoguanidine.

The effects of insulin (5 U/day subcutaneously for 60 days) and aminoguanidine (25 mg./kg./day via gavage for 60 days) on collagen concentration, resistance to enzymatic digestion with Pronase E, and the accumulation of advanced glycosylation end products in bladder tissue were studied in male streptozotocin-diabetic rats. The characteristic autofluorescence of glycosylated connective tissue was used to quantitate advanced glycosylation end products. Fluorescence was measured in digests of bladder tissue and expressed as fluorescence/micrograms. of hydroxyproline. Correlation to alterations in bladder function was made by studying in-vivo bladder micturition and in-vitro length-tension relations of bladder strips. Five groups of age-matched rats were studied: 1) controls, 2) controls treated with aminoguanidine, 3) diabetics, 4) diabetics treated with aminoguanidine, and 5) diabetics treated with insulin. The collagen concentration and the amount of collagen released by enzymatic digestion decreased while the connective tissue autofluorescence increased in bladders from diabetic rats. Insulin was able to prevent all of the observed changes while aminoguanidine protected against changes in accumulation of advanced glycosylation end products and resistance to enzymatic digestion but not against changes in collagen concentration. Stretchability of the bladder as measured by length-tension relations of bladder strips was inversely proportional to the amount of collagen, and therefore increased in diabetic rats. Diabetes of two months duration resulted in altered micturition pattern (increased fluid consumption, diuresis, micturition frequency, and average volume per micturition). Alterations in in-vivo and in-vitro bladder function were prevented by insulin treatment but not by aminoguanidine treatment. We have shown that the collagen component of the bladder wall changes in amount as well as in quality in the diabetic rat. Our data suggest that the amount, rather than the properties of collagen, is important for bladder function.     

Comparative physiology and pharmacology of the cat and rabbit urinary bladder

The cat and the rabbit are two of the most popular models for the study of lower urinary bladder function. The cat has been used extensively for in-vivo studies of spinal and supra-spinal micturition reflexes. In contrast, the rabbit has been used extensively for the in-vitro study of bladder function. In order to determine if the results obtained using one species can be applied to another, we have compared the in-vitro physiology and pharmacology of the cat and rabbit bladder using isolated strips and whole bladder preparations. The results can be summarized as follows: 1) The cat displays significant spontaneous activity during in-vitro cystometry, but the rabbit shows no such activity (whole bladder studies). 2) Although the bladder weights of the cat and rabbit are similar, the rabbit bladder has a capacity three times that of the cat. 3) The maximal response to field stimulation was obtained at one gram of passive tension for the rabbit isolated strips, whereas five grams of passive tension was required for the cat strips. 4) Atropine inhibited the response of isolated strips of cat bladder to field stimulation by approximately 13% whereas the response of rabbit bladder strips was inhibited by approximately 45%. 5) The magnitude of the response of rabbit bladder strips to ATP was similar to the response to field stimulation in the presence of atropine; the response of cat bladder strips to ATP was only 20% of the response of that of the rabbit bladder strips, and approximately 10% of the response of the cat strips to field stimulation in the presence of atropine. 6) Field stimulation produced a 10fold greater rise in intravesical pressure in the cat isolated bladder than in the isolated rabbit bladder; in response to bethanechol, the cat bladder generated a 6-fold greater response than the rabbit bladder. It is clear that the in-vitro pharmacological responses of the cat urinary bladder are qualitatively and quantitatively different from that of the rabbit bladder.     

Effects of sensitization on female guinea pig urinary bladder function: in vivo and in vitro studies

Although bladder inflammation is known clinically to produce a variety of symptoms including urgency, frequency, and pain, there are only a few experimental studies that directly relate bladder inflammation with urodynamic and functional alterations. We have used the sensitized guinea pig model to study the effects of inflammation on micturition parameters, cystometry, and in vitro bladder contractility. This model depends on the allergic response of the bladder mucosa to ovalbumin, an otherwise non-irritative agent, as an antigen. In vivo exposure of the bladder to ovalbumin via urethral catheterization induced a prompt and marked increase in the number of micturitions in antigen-sensitized guinea pigs. Ovalbumin had no effects on the micturition parameters in the control group. Using in vivo cystometry, intravesical exposure to ovalbumin induced a significant decrease in both the pressure at which micturition was induced, and the volume at which micturition was induced. Ovalbumin had no effect on cystometric parameters of the control animals. In vitro exposure of whole-bladder preparations to ovalbumin induced a significant contractile response only in the bladders isolated from the sensitized guinea pigs. The responses of the isolated bladders to field stimulation and bethanechol were identical for bladders from both sensitized and control animals. In conclusion, exposure of the bladder to ovalbumin in the sensitized animal induced an increase in the frequency of micturitions and a decrease in the pressure and volume at which micturition was induced. Thus, intravesical exposure of the bladder mucosa to a substance that the bladder has been sensitized to can induce alterations in micturition that are consistent with the clinical symptoms of "urgency and frequency".     

Effect of ageing on blood flow to the bladder and bladder function.

Ischemia, induced by atherosclerosis, is a common cause of disorders in the elderly. Bladder dysfunction in older people may be caused by detrusor ischemia. We compared blood flow to the bladder and detrusor function in vivo and in vitro in young (6-month-old) and aged (24-month-old) male Sprague-Dawley rats. In both young and old rats, blood flow to the bladder measured by a laser Doppler flowmeter decreased as intravesical volume increased and was smaller in old rats than in young rats. Cystometrograms performed under anesthesia showed that old rats had smaller voiding pressure and larger bladder capacity than young rats. In isolated bladders, the pressure increase in response to bethanechol and low frequency field stimulation were impaired by aging. Volume-pressure studies showed that in isolated bladders of old rats compliance was greater and peak response to field stimulation was observed at a larger capacity. These findings indicate that bladders of older rats have a larger capacity with good compliance, but less contractility. Aging changes correlate with a decrease in blood flow to the bladder.     

Effects of long-term partial outflow obstruction on bladder function in the rat

The effects of chronic partial outflow obstruction in rats were investigated. The urethra of male rats was partially obstructed for 3 or 6 months and bladder function was compared with that of age-matched controls. Bladder function was studied in vivo by infusion cystometry and in vitro by measuring the response of bladder muscle strips to stimulation. Cystometrograms of outflow-obstructed bladders were categorized into three types: type 1 was equivalent to a normal bladder; type 2 was characterized by large capacity, enhanced voiding pressure, and some residual urine; type 3 had the largest capacity, an impaired voiding pressure, and considerable residual volume (overflow-type of incontinence). The type 3 bladder was the most frequently observed type in rats obstructed for 6 months. Bladder weight increased significantly in rats with outflow obstruction. When five in vivo cystometric parameters (pressure at which micturition was induced, capacity, maximum voiding pressure, voided urine volume, and residual urine volume) were analyzed according to duration of obstruction, only two parameters (capacity and residual urine volume) in rats obstructed for 6 months differed significantly from those in age-matched controls. Evaluation of these values according to cystometric type showed a significant deterioration in four of five parameters in type 3 bladders. Contractile responses of the bladder in vitro to field stimulation, bethanechol, ATP, and KCI were significantly impaired in those obstructed for 3 or 6 months. When in vitro responses were analyzed according to the classification of cystometric type, deterioration of contractility was confirmed in both types 2 and 3 bladders. The present animal model of outflow obstruction can serve as a model of benign prostatic hyperplasia in humans. © 1996 Wiley-Liss, Inc.     

Short term functional effects of bladder outlet obstruction in the cat

Experimental bladder outlet obstruction in cats was produced by surgical placement of a silastic cuff around the urethra. Two sizes of cuff were used to produce either moderate or severe obstruction. The following is a summary of the short-term effects on bladder function. Obstruction induced a significant increase in the in vivo voiding pressure, in proportion to severity of the obstruction. There were no significant differences between control and obstructed cats in bladder mass, response of the isolated whole bladder to field stimulation or bethanechol, response of isolated bladder strips to field stimulation, bethanechol and ATP, or muscarinic receptor density in the bladder body. Although there were no differences in bladder mass between control and obstructed bladders, the hydroxyproline concentration of the severely obstructed bladders was significantly reduced. Creatine phosphate concentration was also significantly reduced in obstructed bladders. Although all whole cat bladder preparations displayed spontaneous contractile activity during in vitro cystometry, the obstructed bladders had a greater amplitude and frequency of spontaneous contractions with a lower volume threshold. In addition, the obstructed bladders had a greater tetrodotoxin-resistant contractile response to field stimulation. These results suggest that the obstructed cat bladder can compensate for increased outlet resistance without induction of bladder hypertrophy or significant functional changes, as seen in both rat and rabbit.     

Correlation of in vitro pressure generation with urinary bladder function

Urinary bladder function consists of a filling and storage phase followed by an active coordinated expulsion phase. A large part of our knowledge of bladder function, as well as bladder physiology and pharmacology, comes from a variety of in-vivo and in-vitro experimental animal models. Of the in-vitro methodologies available for the study of bladder smooth muscle, the isolated bladder smooth muscle strip techniques and isolated whole bladder techniques are two of the most popular. In general, the ability to generate pressure in the non-emptying whole bladder model is directly related to phasic contraction of the bladder smooth muscle, and can be equated with the response of isolated strips. Although both techniques generate useful and important information, one must be very careful in making conclusions concerning bladder function based solely on contractile data. We have studied the volume-pressure relationship of the bladders of control rabbits and of those subjected to bladder outlet obstruction (2 week) and unilateral ischemia (2 week). For each bladder, in-vitro cystometry, pressure generation, and the ability of the bladder to empty (in response to both bethanechol and field stimulation) was determined. Although it was clear that outlet obstruction and unilateral ischemia induced marked alterations in bladder compliance, capacity, and the ability to empty, bladder pressure generation was not significantly affected. These studies support the view that contractile studies in and of themselves cannot be used to describe the functional state of the bladder. Only through the application of several techniques including studies on bladder compliance, capacity, and the ability of the bladder to empty can the functional state of the bladder be evaluated.     

Restoration of rat bladder function following release of short- and long-term partial outflow obstruction

Detrusor dysfunction does not recover in some patients with benign prostatic hyperplasia (BPH) even after prostate resection. We studied the functional restoration of the rat bladder after release of short- or long-term outflow obstruction. Bladder function was assessed by in vivo infusion cystometry and an in vitro organ bath technique. There were no significant differences in bladder weight and contractile strength induced by stimuli in detrusor muscle strips from obstructed rats and age-matched control rats. After short-term obstruction the whole bladder pressure generated in vitro by field stimulation, bethanechol, ATP, and KCl completely recovered to control levels. In contrast, after long-term obstruction, the whole bladder pressure in response to field stimulation remained significantly lower than in controls. Infusion cystometry variables, including the pressure at which micturition was induced, maximal voiding pressure, capacity, and residual urine volume, were similar between controls and rats subjected to short-term obstruction. However, the maximal voiding pressure after long-term obstruction was significantly less than that of controls.     

Functional response of the rabbit urinary bladder to anoxia and ischemia

The effects of in-vitro anoxia and in-vivo ischemia on bladder function were studied using the in-vitro whole-bladder model. In addition to assessing the ability of the bladder to empty, this system provides a quantitative measurement of contractile activity. Anoxia was produced by equilibrating the isolated bladder with nitrogen instead of oxygen and ischemia was produced by clamping the arteries supplying the bladder for a period of one hour. The results of these studies can be summarized as follows: (1) The contractile response of the bladder to bethanechol did not decrease until the oxygen tension fell below 20% of normal; below this value the response decreased rapidly. (2) The ability of the bladder to contract declined gradually, as did the intracellular concentration of adenosine triphosphate. (3) The ability of the bladder to empty was lost immediately upon changing to an anoxic medium, as was the ability of bethanechol to produce a sustained contraction. (4) The bladder was able to fully recover from 60 minutes of in-vitro anoxia, whereas 60 minutes of in-vivo ischemia resulted in a permanent reduction in the contractile response to bethanechol.     

Similarities and differences in female and male rat voiding

We measured in adult rats, under anaesthesia, bladder pressure by transvesical cystometry and flow rate by an ultrasound transducer in the distal urethra. The urinary flow was discontinuous in both sexes. No difference between the sexes in bladder pressure oscillations or in non-oscillatory voiding was found but during the oscillatory activity there was a difference in the relationship between bladder pressure and urinary flow. In the female, the bladder pressure decreased when the flow started and increased when the flow decreased resembling species whose urinary flow is continuous. Basically the flow was stable but it was divided into periods of variable duration by full or partial closure of urethral sphincter. In the male rat, the oscillatory flow consisted of short, fast spikes occurring just before the bladder pressure reached the maximum, after which the flow spike decreased slowly. Overall, no differences were seen in bladder pressure data between the genders. However, the maximal flow rate was lower and micturition time was shorter in female rats. When we recorded occasionally occurring micturitions without high-frequency oscillations of intraluminal pressure (IPHFOs) (non-oscillatory voiding), no differences between the genders were seen. The difference during oscillatory voiding between male and female rat can be understood against anatomical and hormonal backgrounds, and by the relative role of rhabdosphincter, which did not activate during non-oscillatory voidings when no differences were detected.     

Cystometrical evaluation of acute and chronic overdistension in the rat urinary bladder

The urodynamic effects of an experimental, partial infravesical outlet obstruction in rats were studied and compared with the effects in sham-operated controls, and in animals that had undergone 24 h of total outlet obstruction. The animals were studied up to 42 days after surgery. Bladder weight increased with time in the partially obstructed group to reach a final value of 6 times that of the control. In water loading experiments micturition volume was unaffected by sham operation. In the partially obstructed bladders it decreased initially but normalized with time. In the group that had undergone 24 h of total obstruction micturition volume also decreased initially but then became significantly higher than in the controls. In cystometry experiments the partially obstructed bladders developed a considerable residual urine and increased threshold and micturition pressures. Detrusor instability was present already after 10 days. Also in the cystometry experiments the bladders that had been totally obstructed for 24 h had increased micturition volumes. Residual volume was only slightly affected by atropine in the control and partially obstructed bladders but increased 7-fold in rats in which the bladder had been totally obstructed for 24 h 42 days previously. We conclude that there is a close relationship between bladder weight, residual volume and micturition pressure in the partially obstructed bladder, and that 24 h of total obstruction results in disturbances of bladder function that might be related to denervation phenomena previously reported by others. Received: 19 February 1997 / Accepted: 18 September 1997     

Selective block of urethral sphincter contraction using a modified Brindley electrode in sacral anterior root stimulation of the dog

AIMS: Patients with spinal cord injury often present with dysfunction of urinary bladder and urethral sphincter. One treatment option is sacral rhizotomy and sacral anterior root stimulation with the Finetech Brindley stimulator. However, a major disadvantage is the lack of selective stimulation, resulting in simultaneous contraction of sphincter and bladder followed by unphysiological micturition. This study investigated the possibility of selective bladder stimulation by using a Brindley electrode. METHODS: In 11 male anaesthetized foxhounds, a complete posterior rhizotomy was perormed. The anterior S2 roots were stimulated with different quasi-trapezoidal (QT) pulses (pulse length range, 600-1,400 microsec; stimulation current, 0.1-2.0 mA; frequency, 20 Hz) by using a tripolar Brindley electrode. Sphincter and bladder pressures were measured urodynamically. RESULTS: All 11 animals showed a maximal reduction of the highest sphincter pressure over 80%, and in 6 of 11 trials, the sphincter pressure was inhibited completely (100%). With stimulations at maximal sphincter blockade, the average achievable bladder pressure was 33.48 cm H(2)O higher than the average sphincter pressure, and in three cases, a strong micturition was observed. Selective blockade of the sphincter was possible by applying QT pulses. The bladders remained uninfluenced by this blockade and kept their excitability at any time. CONCLUSIONS: This study shows that selective bladder stimulation with little or no coactivation of the sphincter is possible. A physiological micturition can be achieved by using a tripolar Brindley electrode. Introduction of this stimulation technique into clinical practice should not face major difficulties, considering that the device is an established electrode.     

Cystometric evaluation of bladder function in non-anesthetized mice with and without bladder outlet obstruction

PURPOSE: To develop a model for cystometric study of bladder function in the awake mouse, and to characterize urodynamically and immunohistochemically the non-obstructed and infravesically obstructed mouse bladder. MATERIALS AND METHODS: Non-obstructed Balb/CJ mice, and mice with bladder outlet obstruction after surgical, partial ligation of the urethra underwent continuous cystometry as previously described for rats. Bladders were also investigated by immunohistochemistry. RESULTS: During the period of cystometry, reproducible micturition patterns were obtained. Marked differences in the urodynamic parameters between non-obstructed and obstructed mice were revealed. In mice subjected to urethral obstruction, micturition pressure (p <0.05), threshold pressure (p <0.05), bladder capacity (p <0.001), micturition volume (p <0.001), and residual volume (p <0.05) increased significantly. There was no difference in basal pressure or compliance between non-obstructed and obstructed mice. Non-voiding bladder activity was consistently recorded in obstructed mice; both frequency and amplitude increased significantly (p <0.01). Compared with non-obstructed bladders, obstructed bladders showed hypertrophy of the bladder wall and various degrees of "patchy denervation" of the detrusor. When tested in non-obstructed mice capsaicin, prostaglandin E2 (intravesical administration) and apomorphine (subcutaneous administration) induced bladder overactivity. CONCLUSIONS: Continuous cystometry can be reproducibly performed in awake, freely moving non-obstructed mice and mice with bladder outflow obstruction. The changes induced by infravesical obstruction in mice were similar to those previously found in rats. This model may be useful for investigations of genetically modified mice.     

Effect of Mucosal Removal on the Response of the Feline Bladder to Pharmacological Stimulation

The urothelium plays an important role in the maintenance of normal bladder function. It provides a nonpermeable barrier to the contents of urine. The urothelium is directly involved in the transduction of both intravesical pressure and intravesical volume information to the afferent nerve fibers located within the lamina propria area. A third function may be to modulate bladder contractile function through local secretion of bioactive substances into the muscularis layers adjacent to the urothelium. To test this last hypothesis, the following experiments were performed: Strips of female cat bladders were isolated from the bladder body, base and urethra. The mucosa of alternate adjacent strips was removed, and the contractile response to field stimulation (FS), bethanechol (body), phenylephrine (base, urethra) and KCl was determined.For the bladder body, the strips without mucosa responded to FS, bethanechol, adenosine triphosphate (ATP) and KCl significantly greater than the strips with mucosa intact. For the bladder base and urethra, the contractile responses to FS, KCl and phenylephrine were significantly greater for the strips with mucosa removed as compared with the strips with mucosa intact. For the urethra and bladder base, FS in the presence of phenylephrine produced a relaxation. For the bladder base, the degree of FS relaxation of the isolated strips with mucosa removed was significantly greater than the strips with mucosa intact. For the urethra, FS relaxation was similar for the two groups. In conclusion, removal of the urethelium significantly and substantially increased the contractile response to FS, KCl, bethanechol and phenylephrine. Field stimulation relaxation in the bladder base was also enhanced. Thus in the cat, the mucosa has a significant inhibitory effect on the contractile response of the bladder to stimulation. The mechanism of this activity is not clear at the present time but will be the subject of further study.     

The functional effect of mild outlet obstruction on the rabbit urinary bladder

Bladder outlet obstruction has been the subject of numerous studies. In previous studies on severe obstruction, the initial response of the bladder has been to produce an acute overdistension of the bladder resulting in severe tissue damage and functional disorders. This is quite different from the slow onset of outlet obstruction seen in association with benign prostatic hypertrophy (BPH). The present study describes the functional effect of mild outlet obstruction created in a rabbit model, and compares it to a previously described model of severe obstruction. Mild bladder outlet obstruction was created by placing a silicon sleeve (inner circumference 30 mm.) around the bladder neck of mature male NZW rabbits. Individual groups of rabbits were studied at one, seven, and 14 days following the creation of the outlet obstruction. The following studies were performed on each group of rabbits: in vivo and in vitro cystometry, field stimulation and cholinergic stimulation using the in vitro whole bladder model. In addition, the tissue concentration of ATP (adenosine triphosphate) and CP (creatine phosphate) and the muscarinic receptor density were determined. The obstructed bladders showed no significant cystometric difference at one day, but revealed a marked decrease of compliance and capacity at one and two weeks. Unlike the response to severe outlet obstruction, there was no initial acute overdistension of the bladder wall. Although the ability of the obstructed bladders to generate intravesical pressure in response to both field stimulation and bethanechol did not decrease, the ability of both forms of stimulation to empty the obstructed bladders was markedly impaired. The response to field stimulation was reduced to a significantly greater extent than the response to bethanechol, indicating neuronal damage. The muscarinic receptor number per bladder was increased above control at all time periods. The intracellular concentration of ATP and CP in the obstructed bladders was similar to that of control. Our present model of mild obstruction was not accompanied by a massive increase in tissue mass nor was there an overdistension of the detrusor; thus, this model would be a more suitable model for the study of clinical outlet obstruction.     

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 (100 mg./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.     

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.     

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 24 hour 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.