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PubMed1990

Comparison of urinary bladder function in sexually mature and immature male and female rats.

Although studies exist using both male and female rats, there are virtually no studies that compare male and female bladder function. In this initial study, in-vivo and in-vitro urinary bladder function was investigated in two age groups of male and female rats (sexually immature and sexually mature). These studies compare in-vivo micturition behavior (water intake, urine output, frequency and volume per micturition); and in-vitro whole bladder function (bladder volume/pressure relationships, the ability of the in-vitro bladders to generate pressure and empty in response to bethanechol and field stimulation). The results can be summarized as follows: 1) The 24 hour water intake, urine output, and volume per micturition for the mature male rats was significantly greater than that of the mature females with no significant differences among the immature females, mature females, or immature males. 2) There were no significant differences in the frequency of micturition between the 4 groups. 3) Although the average plateau pressures (cystometrograms) of the immature and mature female bladders were greater than that of the immature and mature male bladders, the compliance was similar for all groups. 4) The maximum pressure response of the mature female bladder was significantly greater than pressures generated by bladders in the other three groups; there were no age or sex related differences in the bethanechol log ED50 values. 5) There were no age or sex-related differences in the bethanechol log ED50 values or maximal expulsion responses. 6) Field stimulated bladders from mature animals generated significantly greater intravesical pressures than bladders from immature animals, but, there were no significant differences in maximal pressures attained between mature male and female bladders nor between immature male and female bladders. In conclusion, micturition behavior, and the maximal pressure response to bethanechol changed dramatically with sexual maturity. These results are consistent with the idea that estrogen and other hormones may have a marked influence on bladder function and micturition behavior.

Animals↗
PubMed1989

Effect of acute complete obstruction on the rabbit urinary bladder.

Studies on the effect of partial bladder outlet obstruction demonstrate that significant alterations in urinary bladder structure and function occur within 24 hours of the creation of the obstruction. These studies suggest that many of the functional and structural alterations following partial outlet obstruction may result from the initial overdistension which occurs within the first 24 hours. In these present studies, we investigated the time course of the effect of complete obstruction of the rabbit urinary bladder on the contractile response to bethanechol and field stimulation and on the muscarinic receptor density. Male White New Zealand rabbits were divided into five groups: controls, four, eight, 20, and 24 hours of complete obstruction. The results demonstrated that there was a significant decrease in both the contractile response to muscarinic stimulation and muscarinic receptor density at four hours following outlet obstruction (at a time when there was no bladder overdistension). The receptor density and contractile response to stimulation further decreased over the 24 hour period. These studies indicate that the initial decrease in muscarinic receptor density and contractile response to muscarinic stimulation may be mediated in part by the high level of spontaneous contractile activity induced by ligation of the urethra.

Animals↗
PubMed1989

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.

Aging↗
PubMed1989

Functional and pharmacological effects of ureteral diversion.

Urinary diversion is the final therapeutic approach in several bladder pathologies including selected cases of bladder cancer, neurogenic bladder, and painful bladder syndrome. While there have been a few experimental studies on the effects of urinary diversion and subsequent undiversion on bladder capacity, the pharmacological changes occurring with diversion and undiversion have not yet been investigated. Our primary objectives were to determine the functional and pharmacological alterations in the defunctionalized bladder and the effects of refunctionalization on these changes. Thirty-two male adult canines weighing 15 to 20 lb. were used for this study. Three groups of dogs were urine diverted for one, three, and six month durations (four dogs per group). Another three groups of dogs were urine diverted for one, three, and six months (four dogs per group); these dogs were then undiverted for three months. Six control animals received either one or two sham operations at one, three, and six months. In all groups the functional and contractile characteristics of the bladders were assessed by urodynamics and in vitro contractile studies; bladder weight and muscarinic receptor density were also measured. Intravesical capacities determined by in vivo cystometry were reduced significantly to 74%, 63%, and 47% of control values at one, three, and six months respectively after urinary diversion. Bladder capacity returned to above normal levels in bladders diverted and then subsequently undiverted. Similarly, the compliance and bladder weight of the diverted bladders were significantly less than control, while diverted bladders subsequently undiverted were similar to controls. Maximal bladder contractility in response to bethanechol stimulation was less in diverted bladders compared to control. This decrease in contractility was accompanied by a decrease in muscarinic receptor density. After undiversion maximal bladder contractility to bethanechol reached control levels; this was accompanied by a parallel increase in muscarinic receptor density to control values. There was no effect of diversion or undiversion on the maximal response of bladder strips to methoxamine stimulation. Thus, a bladder that has been diverted (defunctionalized) for a period of time showed decreases in capacity, compliance, and contractility to muscarinic stimulation along with a decrease in muscarinic receptor density. All of these parameters were restored after refunctionalization of the bladder.

Animals↗
PubMed1989

Detection of missing vesicoureteral reflux with bethanechol chloride-aided voiding cystourethrography.

Experience in the detection of absent vesicoureteral reflux with bethanechol-aided voiding cystourethrography is presented. The detection rate with conventional contrast-enhanced voiding cystourethrography among 9 study subjects, in whom vesicoureteral reflux otherwise was highly suspected from accompanying clinical, urographic and endoscopic features, and in whom it was absent contralaterally or bilaterally, was improved from 33 per cent (only 3 of 9 patients were positive for reflux) to 100 per cent (all 9 were proved to have vesicoureteral reflux) after bethanechol stimulation. Some representative cases are presented and the mechanisms of inducing vesicoureteral reflux with bethanechol are discussed as well as its clinical relevance. Bethanechol-aided voiding cystourethrography is suggested as a highly sensitive method to detect absent vesicoureteral reflux.

Adult↗
PubMed1989

Lower urinary tract function in the sheep fetus: studies of autonomic control and pharmacologic responses of the fetal bladder.

An experimental preparation was developed to study fetal bladder function. In 16 fetal sheep at 120 days' gestation, two distinct types of bladder contractions were identified, one typical of contractions seen after birth and one phasic. Bladder capacity and intravesical pressure during contraction varied widely among fetuses, but residual urine was invariably less than one ml. Several drugs altered fetal bladder function: bethanechol decreased bladder capacity (6.8 vs. 13.6 ml.); atropine increased bladder capacity (27.3 vs. 6.8 ml.) and resulted in a 17-ml. residual urine; and ritodrine, magnesium sulfate and diltiazem inhibited bladder contractions and also resulted in residual urines of seven, six and seven ml. respectively. The fetal sheep bladder at 120 days' gestation is under both cholinergic and beta-adrenergic control. Further, drugs currently administered to pregnant women for the treatment of pre-term labor and pre-eclampsia cross the placenta and can directly alter bladder function in the developing fetus and the neonate.

Animals↗
PubMed1989

In vitro intravesical instillation of anticholinergic, antispasmodic and calcium blocking agents (rabbit whole bladder model).

The systemic side effects accompanying oral pharmacotherapy of neurogenic bladder dysfunction present significant drawbacks to this type of therapy. In these studies we investigated the effect of intravesical administration of anticholinergic, antispasmodic and calcium blocking agents on pressure response mediated by field stimulation and bethanechol. We used the rabbit in vitro whole bladder model for these experiments. The bladder from a mature male NZW rabbit was mounted in an organ bath as a whole bladder preparation. After control field stimulation and bethanechol stimulation, 20 ml. of saline containing the specific drug being evaluated was instilled into the bladder. At 30 minute intervals, the responses to field stimulation and bethanechol were determined. Two hours after instillation of 100 microM of each specific drug, the inhibition of the contractile response to bethanechol and field stimulation (as % inhibition) was as follows: oxybutynin (95%/64%), verapamil (85%/81%), atropine (68%/31%), diltiazem (47%/39%), and imipramine (44%/47%). Atropine and oxybutynin suppressed the contractile response of the bladder to bethanechol to a much greater extent than that to field stimulation, while verapamil, diltiazem and imipramine suppressed the contractile response to bethanechol and field stimulation to approximately the same extent. Two hours after drug instillation, the intravesical solution was washed out and replaced with saline, but the recovery of the bladder contraction was slow and incomplete. The results of this study suggest that the use of self-intravesical instillation to suppress bladder contractility should be a good therapeutic approach for patients with neurogenic bladder, especially those who are already managed by intermittent catheterization.

Administration, Intravesical↗
PubMed1988

Bethanechol supersensitivity test, rhabdosphincter electromyography and bulbocavernosus reflex latency in the diagnosis of neuropathic detrusor areflexia.

A total of 57 patients with neuropathic or nonneuropathic detrusor areflexia was studied with the bethanechol supersensitivity test, electromyography of the urethral rhabdosphincter and bulbocavernosus reflex latency. The sensitivity of these tests in detecting neuropathic areflexia was 90, 87.5 and 78.1 per cent, respectively, and the specificity was 95.6, 76 and 80 per cent, respectively. When all 3 tests were performed together the combined accuracy approached 100 per cent. These combined tests are useful in the diagnosis of patients with equivocal bladder neuropathic conditions and in those with subtle neurological lesions.

Adolescent↗
PubMed1988

Effect of bethanechol on glycolysis and high energy phosphate metabolism of the rabbit urinary bladder.

The urinary bladder, similar to other smooth muscles, utilizes glucose as one of its primary sources of metabolic energy. We have studied the effect of bethanechol on both glycolysis and high energy phosphate metabolism. The results can be summarized as follows: bethanechol administration in vitro stimulates a 30% decrease in intracellular glycogen, a 100% increase in lactic acid production, and an 80% increase in CO2 generation. Although there was a rapid and sustained decrease in the intracellular concentration of creatine phosphate, there was only a minor decrease in the intracellular concentration of ATP. There were no changes in adenine uptake or de novo ATP synthesis.

Adenine↗
PubMed1986

Effect of age on cholinergic muscarinic responsiveness and receptors in the rat urinary bladder.

The effects of age on urinary bladder responsiveness to muscarinic agonists and on the Bmax and Kd of the binding of [3H]quinuclidinyl benzilate (QNB) to muscarinic receptors of the bladder were studied. Bladder bodies and bases were isolated from Fischer 344 rats, ages seven, 16 and 27 months. No age-dependent change in maximum KCl-elicited isotonic contractions was observed in either bladder region. The bladder base showed an age-dependent increase in the maximum contractions (Emax) elicited by muscarinic agonists. The Emax values for bladder bases from rats 27 months of age were 44 per cent, 58 per cent and 76 per cent greater than those from rats seven months of age for acetylcholine, bethanechol and oxotremorine, respectively. No such alteration in responsiveness was observed in the bladder body with age. There were no age-related changes in ED50 values for the three agonists in either bladder region. Analysis of [3H]QNB binding in the bladder base demonstrated a modest 18 per cent increase in the Bmax (fmol./mg. tissue) from seven to 16 months and a significant 39 per cent decrease from 16 to 27 months. In the bladder body, the Bmax progressively increased by 25 per cent from seven to 27 months. The Kd values of [3H]QNB did not change with age in either region. The data demonstrate that the age-related increase in the responsiveness of the bladder is regionally specific and cannot be explained by a change in the number or affinity of muscarinic receptors.

Acetylcholine↗
PubMed1986

Acute biochemical and functional alterations in the partially obstructed rabbit urinary bladder.

Rapid structural and functional alterations have been noted in several models of partial outlet obstruction. To better characterize the rapid progression of alterations, the partially obstructed urinary bladders of mature NZW male rabbits were studied at 1, 3, 5, 7 and 14 days of outlet obstruction with respect to muscarinic receptor density, DNA, RNA, lipid and hydroxyproline content. Functional characteristics were assessed by measuring the in vitro response of the whole bladder to cholinergic and field stimulation. Wet weight increased eight-fold by day 7, decreasing to four-fold at day 14. Receptor density decreased by 50% by day 1 and remained low throughout. Although DNA concentration varied only slightly from controls, RNA increased four-fold by day 7. Hydroxyproline concentration per mg. tissue decreased in the obstructed bladder, yet total hydroxyproline content of the obstructed bladder significantly increased. Total lipids increased significantly during day 3 through 7 and decreased by day 14. Cystometry revealed a large capacity low pressure system at day 1 which rapidly changed to a low compliance system of lesser volume by day 14. Bladder emptying was significantly impaired in all obstructed specimens. Additionally, electrical field stimulation was significantly less effective than cholinergic stimulation in effecting bladder emptying. The above findings suggest that rapid changes in biochemical parameters occur during the early stage of acute obstruction which may in part be secondary to metabolic or inflammatory alterations in the detrusor. It additionally suggests that the myogenic alterations in partial outlet obstruction are rapid and partially adaptive, while neurogenic alterations appear degenerative and display a lesser degree of short term adaptation.

Animals↗
PubMed1986

Micturition in comatose patients.

The ability to void spontaneously was ascertained in 135 comatose patients, 76 per cent of whom emptied the bladder automatically as soon as the indwelling catheter could be removed. With additional treatment (bethanechol and/or intermittent catheterization), spontaneous micturition was achieved in all of the remaining patients. Elderly men had statistically more difficulties in becoming independent of an indwelling catheter.

Adolescent↗
PubMed1985

Recovery from short-term obstruction of the rabbit urinary bladder.

Partial bladder outlet obstruction is a commonly encountered pathophysiologic state. Recently we have reported on the rapid nature of the contractile and functional changes that occur in the rabbit urinary bladder within one week of chronic partial obstruction. The purpose of this present study is to investigate the ability of the bladder to recover from one week of partial obstruction. Twenty-six mature male white New Zealand rabbits were separated into 3 groups. Each rabbit was anesthetized with ketamine-xylazine and a partial obstruction of the bladder established by gently securing a 2.0 silk suture around the temporarily catheterized bladder neck. The rabbits in group 1 were sacrificed following one week of partial obstruction. For groups 2 and 3, the obstructing suture was surgically removed after one week of obstruction adn the rabbit was allowed to recover for either two or four weeks. At the end of one week of obstruction the bladder displayed a 9-fold increase in tissue mass, 50 per cent reduction in contractile response to bethanechol and a 76 per cent reduction in the ability of the bladder to expel saline. After the two week recovery period, the bladder mass was reduced to approximately twice the control mass, the contractile and pressure responses to bethanechol were returned to control levels, and the ability of the bladder to expel saline recovered to approximately 75 per cent of control levels. No further improvements were observed following the four week recovery period. It appears that although the contractile response recovers completely following the one week obstruction period, the ability of the bladder to empty remains partially impaired.

Adenosine Triphosphate↗
PubMed1985

Effects of metoclopramide on detrusor function.

Metoclopramide (Reglan) has been widely used as a motility agent because of its contractile effects on gastrointestinal smooth muscle. This agent also may demonstrate significant effects in the urinary system; however, controlled studies of possible effects on bladder function have not been previously reported. Metoclopramide effects on the detrusor smooth muscle were studied using a canine model system. Metoclopramide was compared with bethanechol chloride and a control substance in a random double blind study. Preliminary data from this animal model suggests that metoclopramide significantly increased detrusor contractility as manifested by a decrease in bladder capacity, an increase in detrusor peak voiding pressure and a decrease in post-void residual volume. These effects were similar to those manifested by parenteral bethanechol chloride.

Animals↗
PubMed1985

Effect of acute selective sacral rhizotomy in cats on bladder and urethral function and the response to bethanechol chloride.

Bladder and urethral responses to filling and to subcutaneous bethanechol are dependent upon intact sacral innervation. Acute selective sectioning of nerve roots in chloralose anesthetized cats was used to compare the sacral innervation requirements for the support of these responses. The detrusor was found to require primarily intact S2 roots although an S2 root on one side could, alone, subserve a weak, unsustained detrusor reflex. The urethral reaction to bladder filling required an afferent sacral pathway through either S1 or S2 roots. The sustained bladder response to subcutaneous bethanechol required greater sacral innervation than the detrusor reflex inasmuch as the S2 segment could subserve this response in only half the cases, and unilateral rhizotomy L7-S3 eliminated the response in half the cases. Both treatments, however, were compatible with a preserved detrusor reflex. The urethral constriction response to subcutaneous bethanechol required an intact sacral afferent pathway through either the S1 or S2 segments. In conclusion, the detrusor and urethral reflex responses to bladder filling and subcutaneous bethanechol require a certain amount of intact sacral innervation through S1 and S2 which is least for the detrusor reflex and greatest for the bladder response to subcutaneous bethanechol.

Animals↗
PubMed1985

Bladder and urethral function and supersensitivity to subcutaneously administered bethanechol in cats with chronic cauda equina lesions.

The failure of bethanechol chloride to induce voiding in patients with neurogenic bladder, despite a positive bethanechol test, is being reported more frequently. An experimental model was designed in the cat to study the response of the bladder and urethra to subcutaneous and intraarterial bethanechol after complete and partial sacral decentralization. Complete sacral rhizotomy abolished the micturition reflex. Basal urethral perfusion pressure was not affected by complete sacral rhizotomy and a significant part of this basal urethral pressure remained sympathetically mediated. However, the urethral constriction response to bladder filling was lost in half the cats with complete lesions. Bladder and urethral supersensitivity to bethanechol chloride in cats with complete lesions was characterized by a shift to the left of the i.a. dose-response curve, and by the presence of responses to doses of s.c. bethanechol chloride which are subthreshold in normal cats. The urethra also showed exaggerated constriction responses to i.a. and s.c. bethanechol. After complete lesions a part of the bladder and urethral responses to s.c. bethanechol was adrenergically mediated and exerted through the vesicourethral short neuron system. The rest of the response was due to stimulation of urethral muscarinic receptors. Partial sacral lesions were compatible with a micturition reflex and the urethra retained its reflex response to bladder distension. After partial decentralization the bladder and urethra also showed responses to subthreshold doses of s.c. bethanechol. While the bladder response to s.c. bethanechol did not show a significant adrenergic component in cats with partial lesions, most of the urethral response was sympathetically mediated. In conclusion, complete cauda equina lesions result in an areflexic detrusor with frequent loss of the urethral responsiveness to bladder filling. Urethral supersensitivity to s.c. bethanechol might be responsible for a non-voiding outcome after bethanechol injection in patients with complete cauda equina lesions, despite a positive bethanechol test. Because the detrusor reflex is preserved and the urethra is less supersensitive to bethanechol after partial cauda equina lesions, these may represent a better indication for bethanechol therapy than do complete ones.

Animals↗