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P A Longhurst

Publications and source records attributed to P A Longhurst.

At least 55 records · Page 3Linked to original sources

Effect of slow and rapid cystometry on in vitro rat urinary bladder DNA synthesis.

1. Partial outflow obstruction induces marked changes in detrusor contractile function and morphology. One common finding in all experimental animal models of partial outflow obstruction is a significant increase in bladder mass. 2. Previous studies have demonstrated that partial outlet obstruction induces a rapid and substantial increase in [3H]thymidine incorporation into virtually all cellular elements of the bladder. 3. The present study was designed to investigate the [3H]thymidine uptake and localization induced by exposure of the in vitro whole rat bladder model to various intravesical pressures and rates of intravesical infusion. 4. The results are as follows: (a) There were no differences in DNA concentration between control and other groups. (b) Slow infusion induced a mild increase in DNA synthesis ([3H]thymidine incorporation) at 0.5 ml and a significantly greater level of DNA synthesis at 1.6 ml. (c) [3H]thymidine incorporation was significantly increased by exposure to 7.5 cm H2O, 15 cm H2O, and 30 cm H2O. (d) Exposure to 60 cm H2O and 90 cm H2O did not initiate an increase in [3H]thymidine incorporation. (e) Autoradiography showed that all tissue elements (urothelium, connective tissue, smooth muscle) participated in the response.

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Modulation of urinary bladder function by sex hormones in streptozotocin-diabetic rats.

The modulation of urinary bladder function by sex hormones was examined in castrated and sham-operated male and female streptozotocin-diabetic rats. Male and female diabetic rats weighed less than age-matched controls and had significantly greater serum glucose levels and bladder weights. Castration had no effect on bladder mass and did not alter the diabetes-induced changes in rat or bladder mass. Protein concentrations were significantly increased and collagen concentrations were significantly decreased in bladders from diabetic rats compared with non-diabetics. Sex or castration had no effects on protein or collagen concentration of bladders from nondiabetic and diabetic rats. There were no differences in water consumption and urine excretion between male and female nondiabetic rats, and no effects of castration were observed on micturition in nondiabetic rats. Ovariectomy followed by diabetes caused a significant increase in urine excretion compared with diabetes alone. Ovariectomized diabetic rats had increased mean and maximal micturition volumes when compared with other female rats. Orchiectomy had no effects on the expected increases in micturition associated with diabetes. Diabetes in male rats caused significant increases in contractile responses of bladder strips to field stimulation, carbachol, KCl and high concentrations of ATP. In both nondiabetic and diabetic groups, orchiectomy had no effects on the contractile responses compared with sham operation. Similarly, in bladder strips from diabetic females, contractile responses to carbachol, KCl and high concentrations of ATP were significantly increased compared with those of nondiabetics, and were unchanged by ovariectomy. However, ovariectomy in nondiabetic rats caused significant decreases in contractile responsiveness to nerve stimulation, effects which were only partially prevented by diabetes. The data suggest that there are few differences between male and female rats in their sensitivity to streptozotocin and the effects of diabetes on micturition, bladder collagen and protein concentration, and the responsiveness of bladder strips to contractile agents. The changes in bladder function observed after induction of diabetes do not appear to be related to changes in sex hormone levels. The major differences noted between males and females were the decreased responsiveness of bladders from nondiabetic ovariectomized female rats to field stimulation. In conjunction with previous data obtained in this laboratory, the study suggests that the responses to field stimulation are more sensitive to the effects of ovariectomy than are the responses to contractile agonists.

Adenosine Triphosphate↗

Comparison of urinary bladder function in rats with hereditary diabetes insipidus, streptozotocin-induced diabetes mellitus, and nondiabetic osmotic diuresis.

In vivo and in vitro bladder function were studied in three different models of increased diuresis: 1) Brattleboro rats with hereditary diabetes insipidus (di/di), 2) Sprague-Dawley rats with streptozotocin-induced diabetes mellitus (STZ), and 3) Sprague-Dawley rats with increased diuresis due to 5% sucrose added to the drinking water. When compared with controls, all three models showed bladder mass, increased water consumption and urine output, higher mean and maximal increased micturition volumes, and greater bladder capacity and compliance by in vitro cystometry. The changes were more extensive in di/di rats than in the STZ and sucrose-drinking rats. The concentration of bladder collagen decreased in all three rat models when compared with controls. However, the collagen concentration of STZ bladders was significantly lower than the collagen concentration of di/di and sucrose bladders, suggesting that the decrease in bladder collagen concentration associated with experimental diabetes mellitus is only partly related to the increased diuresis. Contractile function was studied using a whole bladder model. Responses of whole bladders from control and diabetic rats to electrical field stimulation, carbachol and KCl were identical. Volume-pressure relations of the isolated whole bladder showed that the magnitude of the contractile response to KCl is constant at intravesical volumes ranging from about 10 to 95% of cytometrical bladder capacity. Bladders from Brattleboro di/di rats and STZ rats showed a rightward shift of volume-passive pressure curves when compared with appropriate controls. Bladders from sucrose-drinking rats had volume-passive pressure curves similar to the bladders from controls. This study suggests that while contractile function remains intact with increased diuresis, the passive function changes, with the bladder becoming more distensible.

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Temporal changes in rabbit urinary bladder function and DNA synthesis during chronic treatment with furosemide.

In a preliminary study we showed that 14 days of furosemide infusion in rabbits caused increases in bladder mass and contractile responses of bladder body strips to field stimulation, bethanechol, ATP and KCl. The present study investigated the temporal effects of furosemide-induced diuresis on micturition, bladder mass, bladder wall proliferation activity and DNA synthesis. In addition, contractile responses of bladder body strips were monitored. Furosemide-containing osmotic pumps were implanted in male New Zealand White rabbits. Micturition was monitored for 7 days. Biochemical analyses were done 3, 7 and 14 days after implantation. Contractile responses were measured at 3 and 7 days. Polyuria and polydipsia started within 1 day after implantation of furosemide-containing osmotic pumps and continued at the same level for 7 days. Bladder mass was significantly increased at 3 and 7 days. Diuresis stimulated 3H-thymidine uptake and caused an increase in bladder DNA concentration at 3 days. However, both DNA concentrations and 3H-thymidine levels returned to control levels by 7 days. Contractile responses to field stimulation and agonists were increased at 7 days but unchanged at 3 days. The data confirm that modest increases in bladder mass and the ensuing increases in contractile function are a normal and beneficial physiological response to diuresis.

Adenosine Triphosphate↗

Factors underlying the increased sensitivity to field stimulation of urinary bladder strips from streptozotocin-induced diabetic rats.

1. The responses of bladder strips from control, streptozotocin-diabetic, and sucrose-drinking rats to electrical field stimulation were investigated. Sucrose-drinking rats were included as additional controls because they have enlarged bladders as a result of non-diabetic diuresis. 2. Bladder strips from diabetic rats developed more spontaneous activity than those from the two control groups. Indomethacin reduced the amplitude and frequency of spontaneous contractions suggesting that they resulted from endogenous prostaglandin formation. Tetrodotoxin (TTX) had little effect, while alpha, beta-methylene ATP caused increases in spontaneous activity. 3. Bladder strips from diabetic rats responded to field stimulation with greater contractions than controls in the absence of antagonists as well as in the presence of atropine and alpha, beta-methylene ATP. Increasing TTX concentrations caused a step-wise depression of the contractile response to electrical stimulation which was not affected by preincubation with either atropine or alpha, beta-methylene ATP. 4. Atropine and indomethacin had no effect on strength-duration curves constructed to measure threshold contractile responses to five pulses stimulation. The curves were shifted to the right by both TTX and alpha, beta-methylene ATP, indicating that the responses were neurogenic in nature and at least partially, the result of stimulation of P2-purinoceptors. In the absence of drugs, bladder strips from diabetics responded at lower voltages and pulse widths than those of control and sucrose-drinking rats, suggesting that they were more excitable. 5. The response curve of bladder strips from diabetics to field stimulation at increasing voltage was shifted upwards and to the left compared to strips from control or sucrose-drinking rats. 6. Bladder strips from diabetics responded to stimulation at increasing pulse width with greater responses than those from control or sucrose-drinking rats. At 1.0 ms pulse width, the TTX-resistant response of strips from diabetic rats was still greater than that of the other groups, indicating that a myogenic component was also involved.7. The data suggest that bladder strips from diabetic rats are more excitable than those of control or sucrose-drinking rats. This may result from diabetes-induced decreases in bladder lipid or other membrane changes, and/or be a result of partial depolarization, perhaps related to diabetic neuropathy.

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Metabolic studies on rabbit bladder smooth muscle and mucosa.

Recent studies indicate that the mucosa of the urinary bladder may play a major role in the maintenance of normal bladder function. The mucosal surface of the urinary bladder serves as a protective layer against the irritative solutes found in the urine. The integrity of this barrier can be broken by overdistension, anoxia, detergents, alcohols, bacterial infection and by contact with agents to which the mucosa has been sensitized. In view that both anoxia and ischemia can mediate a breakdown in the role of the mucosal layer as a permeability barrier, it is reasonable to assume that this function is dependent on cellular metabolism. As an initial investigation we have compared a variety of biochemical and metabolic parameters between the mucosal layer (consisting of the lamina propria, urothelium, and any connective tissue and vascular tissue within this layer); and the muscularis layer. The results of these studies demonstrated that the rate of glucose metabolism to lactic acid (LA) of the mucosa was more than three-fold greater than that of the smooth muscle. The rate of CO2 production of the mucosa was 60% greater than that of the unstimulated smooth muscle. The maximal activity of the mitochondrial enzyme citrate synthase was significantly greater in the mucosa than in the smooth muscle, however, the activity of malate dehydrogenase was similar for both tissues. The maximal activity of the cytosolic enzyme creatine kinase was more than two-fold greater in the bladder smooth muscle than in the mucosa; although the affinities of the creatine kinase isoforms of the mucosa were significantly greater than those of the muscle.(ABSTRACT TRUNCATED AT 250 WORDS)

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Regulation of adrenal and hepatic alpha-tocopherol content by androgens and estrogens.

Previous studies demonstrated that alpha-tocopherol concentrations were far greater in adrenal glands and in livers from female rats than in those from males. Studies were done to investigate the role of androgens and estrogens in the regulation of adrenal and hepatic alpha-tocopherol content. In males and females, adrenal concentrations of alpha-tocopherol were approx. 10-fold greater than those in liver and the highest concentrations of alpha-tocopherol were in the crude mitochondrial fractions in both organs. Castration of female rats decreased alpha-tocopherol concentrations in adrenals and in livers. Proportionately similar declines occurred in both organs and in all subcellular fractions. The effects of castration were prevented by estradiol replacement at the time of surgery. Gonadectomy in male rats had effects opposite to those in females, increasing adrenal and hepatic alpha-tocopherol concentrations. Testosterone administration to castrated males prevented the increases in adrenal and hepatic alpha-tocopherol content. Neither castration nor gonadal hormone replacement in either sex had any effect on plasma alpha-tocopherol levels or on cytosolic ascorbic acid concentrations in adrenals or livers. The results indicate a role for estrogens and androgens in the regulation of adrenal and hepatic concentrations of alpha-tocopherol. The opposing effects of androgens and estrogens fully account for the sex differences in tissue alpha-tocopherol levels in rats.

Adrenal Glands↗

The influence of diabetes mellitus on glucose utilization by the rat urinary bladder.

Streptozocin-induced diabetes in rats causes changes in urinary bladder function and increases the responsiveness of isolated bladder strip preparations to contractile agents and field stimulation. We monitored the role of extracellular glucose in the contractile responsiveness of bladder body strips from control, 2-month diabetic, and sucrose-drinking rats to the muscarinic agonist bethanechol. Consumption of sucrose and induction of diabetes caused increases in bladder mass compared with that of controls. In the presence of normal glucose levels (5.6 mmol/L), bladder strips from diabetic rats responded to bethanechol with significantly larger responses than those from control or sucrose-drinking rats. Removal of glucose from the bathing medium caused time-dependent decreases in contractile response of bladder strips from all groups; there were no differences in the percent decrease in response between the three groups. The presence of insulin (100 mU/mL) had no effects on contractile responsiveness or the rate of decline of response. Following return of glucose to the medium, there were progressive increases in contractile responsiveness in all groups, which returned to original contractile values within 60 minutes and were unaffected by insulin. Pyruvate (9.1 mmol/L) was able to substitute for glucose in maintaining the contractile responses. Increasing the glucose concentration of the medium to 30 mmol/L had no effects on contractile responses. Unstimulated bladder adenosine triphosphate (ATP) and creatine phosphate concentrations were similar in control, diabetic, and sucrose-drinking rats. In conclusion, changes in glucose utilization and high-energy phosphate levels cannot explain the increased contractile responsiveness of bladder body strips from diabetic rats to contractile agents.

Adenosine Triphosphate↗

Effect of potassium on the contractile response of the rat detrusor muscle to field stimulation at increasing calcium concentrations.

1. At 0.6 and 1.8 mM calcium, increasing the potassium concentration from 2.5 to both 7.5 and 12.5 mM significantly increased the contractile response to field stimulation at 0.5, 1, 2 and 4 Hz. There were no effects on the contractile responses to 8, 16, 32 and 64 Hz. 22.5 mM potassium significantly reduced the contractile response to all frequencies of stimulation. 2. At 5.4 mM calcium, the contractile responses to all frequencies in the presence of 2.5, 7.5 and 12.5 mM potassium were similar. The responses to all frequencies of stimulation in the presence of 22.5 mM potassium were significantly reduced. 3. In general, the relative responses to low frequencies of stimulation were significantly greater in the presence of 5.4 mM calcium than in the presence of 0.6 or 1.8 mM calcium. 4. The magnitude of the inhibition in the presence of 22.5 mM potassium was inversely proportional to the extracellular calcium concentration, i.e. the lower the calcium concentration, the greater the inhibition. 5. The bladder base responded to alterations in the potassium and calcium concentrations similarly to the bladder body. 6. In conclusion, increasing the potassium concentration from 2.5 mM (normal bath concentration) to 7.5 and 12.5 mM significantly enhanced the contractile response to low frequency stimulation at both 0.6 and 1.8 mM (normal bath concentration) calcium.

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The effect of furosemide-induced diuresis on rabbit micturition and bladder contractile function.

The morphology and contractile function of the urinary bladder can be significantly altered in response to specific forms of physiological and pathophysiological stress placed upon it. For example, partial outlet obstruction results in a marked increase in bladder mass (weight) with associated alterations in the contractile response to specific forms of stimulation. Diabetes and its associated diuresis also induce significant alterations in bladder weight and contractile function. The current study was designed to determine if the increase in bladder weight induced by diuresis is associated with contractile alterations similar to those observed following partial outlet obstruction. Diuresis was induced by continual slow-infusion of furosemide using osmotic pumps. The results can be summarized as follows: 1) After two weeks of furosemide treatment the bladder mass was significantly greater than in the controls. 2) Furosemide-treated rabbits consumed and excreted three times more fluid than did the controls. 3) In vivo cystometric capacity and bladder compliance of the furosemide-treated rabbits were significantly increased. 4) Diuresis induced a significant increase in the contractile response of isolated bladder body strips to field stimulation, ATP, bethanechol, and KCl. 5) Furosemide treatment had no effects on the contractile responses of bladder base strips to any form of stimulation. Diuresis resulted in a significant increase in bladder weight and an associated increase in the contractile state of the bladder body, presumably through an increase in smooth muscle.

Adenosine Triphosphate↗

Effects of partial outlet obstruction of the rat urinary bladder on micturition characteristics, DNA synthesis and the contractile response to field stimulation and pharmacological agents.

Partial outlet obstruction is one of the major urological complications induced by benign prostatic hypertrophy (BPH). The current study describes the time course of the effect of mild partial outlet obstruction (in rats) on in vivo micturition parameters, DNA synthesis, and on the in vitro response of the bladder to field stimulation, bethanechol, methoxamine, ATP, and KCl. Mild partial outflow obstruction was created by placing a catheter (outside diameter: 1.70 mm.) transabdominally in front of the urethra, tying a ligature (2-zero silk) around both the urethra and catheter, and then removing the catheter. The micturition pattern was monitored for 2 days prior to surgery, and then continuously for 14 days following the surgery. The changes in bladder weight and the in vitro detrusor function of control (sham operated) and obstructed bladders (1, 3, 5, 7, 14 and 28 days after surgery) were examined. Micturition frequency in the dark cycle decreased immediately after the operation, and then increased linearly reaching a maximum at the 5th day, and stabilized at this increased level for the duration of the micturition study. The frequency of the dark cycle was also decreased immediately after the sham surgery and then gradually increased over the period of observation. Bladder weight increased by day 1 following surgery, and remained high throughout the 28 day study. The contractile response of the obstructed bladder base to field stimulation was reduced at days 1 and 3. The response then increased above control for day 5, reached a maximum response at day 7 and remained at this level for days 14 and 28. A similar pattern was observed for the contractile response of the bladder body to bethanechol and KCl, and for the bladder base to methoxamine and KCl. Both obstructed and sham surgeries increased bladder DNA content and 3H-thymidine incorporation, which reached maximal values on days 5 and 3, respectively. DNA content and 3H-thymidine incorporation of obstructed bladders were greater than those of sham operated bladders. In conclusion, partial outlet obstruction in the rat resulted in a progressive increase in bladder mass, an increase in micturition frequency, increases in the in vitro contractile response to field stimulation, bethanechol, methoxamine, and KCl, and increases in bladder DNA content and 3H-thymidine incorporation.

Adenosine Triphosphate↗

3H-thymidine uptake by the rat urinary bladder after induction of diabetes mellitus.

Streptozotocin-induced diabetes mellitus causes diuresis, increases in bladder mass and changes in micturition. Temporal changes in micturition and bladder mass after induction of diabetes with streptozotocin were monitored and correlated with DNA synthesis and 3H-thymidine incorporation. There were increases in water consumption, urine excretion, urinary frequency, and mean and maximal micturition volume within 1 day after induction of diabetes. These parameters reached maximal values within 6 to 11 days and were maintained at 30 and 60 days. Bladder mass was significantly elevated by 7 days and did not increase further with increasing duration of diabetes. DNA concentration was decreased in bladders from 4, 7 and 14 day diabetics. 3H-thymidine incorporation into DNA increased within 2 days after induction of diabetes, reached maximal values at 4 to 7 days and declined to control values by 14 days. Autoradiography showed intense labelling of the urothelium one day after induction of diabetes, with labelling remaining high up to day 7. Connective tissue and smooth muscle labelling were slower to develop. Labelling of smooth muscle was transient, appearing only on days 4 and 7. The time course of the events was consistent with the hypothesis that bladder distension or increasing micturition volume stimulates thymidine incorporation into DNA, resulting in an increase in bladder mass.

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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.

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The influence of streptozotocin-induced diabetes mellitus on the sensitivity of rat urinary bladder body and base strips to changes in extracellular calcium.

1. The influence of calcium on contractile responses of bladders from control and 2 month streptozotocin-diabetic rats was investigated. 2. Removal of calcium from the bathing medium caused rapid decreases in the contractile responses of bladder body and base strips to carbachol. The responses of strips from control rats were reduced more by calcium removal than were strips from diabetics. 3. Replacement of calcium caused dose-dependent increases in contraction to carbachol. The responses of bladder body strips from diabetic rats to carbachol were significantly greater at all calcium concentrations than were those of controls. There were no differences in the responsiveness of bladder base strips to carbachol. 4. In contrast, bladder body strips from diabetic rats were more sensitive to calcium than were strips from controls, with an IC50 value for calcium of 0.38 mM vs 0.72 mM for controls. 5. At the calcium concentration of Krebs buffer (2.5 mM), contractile responses were near maximal, and there were no differences in sensitivity. 6. The calcium antagonist nifedipine caused dose-dependent decreases in the contractile responses of bladder base and body strips to nerve stimulation. The responses to nerve stimulation were more sensitive to nifedipine than were those to carbachol. There were no differences between controls and diabetics in the sensitivity of bladder strips to nifedipine. 7. The findings suggest that although increases in sensitivity to calcium are observed in bladder body strips from streptozotocin-diabetic rats, they are unlikely to be responsible for the increases in maximal contractile response to nerve stimulation and contractile agents.

Animals↗

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.

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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.

Adenosine Triphosphate↗

Studies on experimental bladder outlet obstruction in the cat: long-term functional effects.

Experimental bladder outlet obstruction in cats induces a significant increase in the in vivo leakage pressure. The effects of obstruction on the detrusor function were analyzed, using control, 3, 6 and 12 month obstructed cats. The in vivo leakage pressures were substantially increased in all obstructed groups. From a previous study on the short-term effects of obstruction in the cat; although there was an immediate increase in pressure, there were no significant differences between control bladders and two week obstructed bladders in: bladder weight, peak pressure response to field stimulation and bethanechol, and emptying of the in vitro whole bladder model. In this current study, although there was no direct relationship between duration of obstruction and severity of the impaired pharmacological response of the isolated whole bladder, there was a direct relationship between the magnitude of the increase in bladder weight, leakage pressure, and impaired functional response of the in vitro whole bladder. In this regard the cats were separated into four groups: controls and shams (average bladder weight 2.95 gm.), obstructed group 1 with bladder weights less than 6.0 gm. obstructed group 2 with bladder weights between 6 and 10 gm., and obstructed group 3 with bladder weights greater than 10 gm. The results can be summarized as follows: A) In vivo leakage pressures were significantly increased in all obstructed groups, and progressively higher in proportion to the bladder weights. B) Bladder capacity significantly increased in all, being greatest in obstructed group 3. C) The magnitude of the response to field stimulation of obstructed groups 1 and 2 were significantly greater than the response of control bladders at virtually all frequencies. The frequency response curve of obstructed group 3 was similar to control. D) The ability of the bladder to empty in response to field stimulation was significantly reduced in all obstructed groups. The magnitude of the decrease was proportional to the increase in bladder weight. E) There were no differences between control and obstructed bladders in the pressure response to bethanechol or KCl; the ability of both bethanechol and KCl to empty the bladder was reduced in the obstructed groups. In general, the presence of bladder enlargement was accompanied by significant alterations in the ability of the in vitro bladder to empty in response to field stimulation, bethanechol, and KCl.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗