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Biomedical subjects

R M Levin

Publications and source records attributed to R M Levin.

At least 145 records · Page 8Linked to original sources

A novel canine model of partial outlet obstruction secondary to prostatic hypertrophy.

Benign prostatic hyperplasia (BPH) is a major medical problem in the United States. The primary medical complication of BPH is progressive obstruction of the urethra and a subsequent in reduction the ability or the bladder to empty efficiently. The urodynamic characteristics associated with BPH include hyperreflexia, increased bladder capacity, increased frequency, decreased flow rate, and increased residual volume. Although there currently are individual animal models of prostate enlargement and animal models of partial outlet obstruction, there is no model of progressive obstruction secondary to prostate enlargement. The primary objective of the current study was to develop a canine model of BPH that would secondarily result in partial urethral obstruction and impaired urodynamics. Our model consists of encapsulating the prostate in a nylon mesh to prevent the growth of the prostate into the peritoneal cavity and then treating the dog with steroids to induce prostate growth and subsequently produce urethral constriction. The results demonstrate that encapsulation of the dog prostate and administration of steroids results in an increase in prostate mass simultaneously with an increase in urethral pressure and in changes in bladder contraction consistent with the presence of partial outlet obstruction. This preliminary study demonstrates that by preventing the outward growth of the steroid-stimulated prostate, urethral obstruction resembling BPH can be produced.

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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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Biphasic response of the rabbit detrusor muscle to changing the extracellular concentrations of potassium and calcium.

1. In the presence of 1.8 mM calcium (normal Tyrode's solution) increasing the potassium concentration significantly enhanced the phasic response of the rabbit detrusor muscle to 1 Hz field stimulation but did not affect either the tonic tension or the maximal rate of contraction. 2. At low calcium (0.6 mM) increasing the potassium concentration enhanced the phasic response to 1 and 4 Hz and significantly increased the tonic tension and the rate of tension generation. 3. Increasing the extracellular calcium concentration enhanced all parameters in a dose-dependent manner at all frequencies. The effect of increasing calcium was significantly greater at 1 and 4 Hz than at 32 Hz. Surface spectrofluorometry demonstrated that the increase in intracellular calcium stimulated by field stimulation paralleled the phasic contractile responses. 4. These results can be explained by potassium-induced increases in the intracellular bound calcium.

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Effect of partial outlet obstruction of the rabbit urinary bladder on ryanodine binding to microsomal membranes.

1. Partial outlet of obstruction of the rabbit urinary bladder results in a significant increase in the ability of ryanodine to inhibit field stimulated contraction. The current study determined the effect of outlet obstruction on ryanodine binding to microsomal membranes. 2. The results demonstrate: (i) Ryanodine binding is linear showing one set of ryanodine binding sites (Bmax = 28 +/- 3.5 fmol/mg protein; Kd = 4.2 nM). (ii) Total ryanodine binding was slightly increased at 1 and 3 day following obstruction. (iii) Binding increased approx 4-fold at 5 and 7 days post obstruction. (iv) No change in the Kds were noted at any time period. 3. The results of these studies indicate that smooth muscle hypertrophy secondary to partial outlet obstruction induces a marked increase in the role of intracellular calcium in the mediation of the contractile response to field stimulation.

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Developmental aspects of excitation contraction coupling of rabbit bladder smooth muscle.

There is growing evidence that smooth muscle function changes with normal development. In this study a Scatchard analysis revealed that the binding of 3H-ryanodine changed from 6.6 fmol./mg. protein in 3-day-old rabbits to 44 fmol./mg. protein in 8-week-old rabbits (p < 0.05) with no associated developmental changes in the dissociation constants. The physiological findings using muscle strip techniques correlate well with these findings in that the neonatal bladders are far less sensitive to ryanodine than their mature counterparts. In contrast, nifedipine inhibited contractility in the neonatal group to a much greater degree than the mature group. These biochemical and physiological findings support our contention that the mechanism for excitation contraction coupling changes with normal development. Contraction in neonatal rabbit bladder smooth muscle is more dependent upon the influx of extracellular calcium and with normal maturation mechanisms for intracellular calcium storage and release begin to predominate.

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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↗

Anoxia and corporal smooth muscle dysfunction: a model for ischemic priapism.

The hemodynamics of penile flaccidity, erection and detumescence requires corporal smooth muscle to function across a wide variation in pO2. The present study describes the effect of anoxia on corporal smooth muscle response to field stimulation and pharmacologic agonists and antagonists of erection. The response of isolated strips of rabbit corpus cavernosal tissue to field stimulation, phenylephrine, bethanechol, ATP and KCL was determined under oxygenated and anoxic conditions. The results can be summarized as follows: 1) Anoxia eliminated spontaneous contractile activity and reduced basal tissue tension to a minimum. 2) Neither field stimulation nor pharmacological agents (ATP, bethanechol, isoproterenol) could relax basal tension below that induced by anoxia alone. 3) Under anoxic conditions alpha-adrenergic agonists produced poorly sustained phasic contractile responses; anoxia eliminated tonic contractile responses to phenylephrine. 4) In normoxic conditions field stimulation of smooth muscle precontracted with phenylephrine produced frequency-dependent graded relaxations; under anoxic conditions field stimulation yielded contractile responses at all frequencies. Our data suggest that corporal smooth muscle tone, spontaneous contractile activity, the contractile response to alpha-agonists and field stimulated relaxation depend on the state of corporal oxygenation. The inability of alpha-stimulation to induce a tonic contraction of corporal smooth muscle under anoxia in vitro parallels the failure of penile injection of alpha-adrenergic agonists to relax ischemic priapism.

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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↗

Comparative studies on the ontogeny and autonomic responses of the fetal calf bladder at different stages of development: involvement of nitric oxide on field stimulated relaxation.

This initial study correlates the passive length-tension relationship, contractile and relaxant responses to field stimulation and contractile responses to specific autonomic agonists and antagonists with gestational age. Fetal bovine bladders were separated into three groups based on the head-rump length (FL): 30 to 45 cm. (early gestation), 50 to 65 cm. (middle gestation) and 70 to 85 cm. (late gestation). Each bladder was separated into upper and lower bladder segments; longitudinal strips of smooth muscle were isolated and placed in individual muscle baths. Passive length-tension studies demonstrated that compliance was greatest in the bladder of late gestation and lowest in the bladder of early gestation period. Field stimulation (FS) elicited frequency-dependent contractile responses in all strips. In the upper bladder, the maximal response and maximal rate of tension generation to FS was lowest in the youngest fetuses and increased in proportion to the gestational age. In the lower bladders, there were no gestational age-related differences in the maximal response or maximal rate of tension generation in response to field stimulation. The maximal response of the upper bladder to bethanechol increased significantly from the youngest gestational age to mid-gestation, with no further changes between mid- and late gestation. The maximal response to field stimulation and bethanechol were equal between upper and lower bladder segments for the youngest gestational bladders, whereas for the oldest gestational ages, the maximal response of the upper bladder to FS and bethanechol were significantly greater than the responses of the lower bladder. In the presence of maximal precontraction with bethanechol, FS induced a rapid and marked decrease in tension. The magnitude of the relaxation was substantially greater for the strips of lower bladder than for the strips of upper bladder at late gestation. In lower bladders, the magnitude of the field stimulated relaxation was greater in the strips from the older fetuses than in the strips from younger fetuses. In all strips, field stimulated relaxations were completely inhibited by pretreatment with L-NAME (an inhibitor of nitric oxide synthesis), indicating that the FS-induced relaxation was due to nitric oxide. In addition to nitric oxide-induced relaxation, beta adrenergic stimulation also induced a significant relaxation of the isolated strips. In summary, these data suggest that, in the tubular shaped fetal bovine bladder, there were distinct differences in the autonomic responses between the upper bladder segment and the lower bladder segment in the late gestation period.

Adenosine Triphosphate↗

Developmental changes in normal fetal bovine whole bladder physiology.

In the present study, normal and experimentally altered whole fetal bovine bladders have been used in vitro to study developmental changes in compliance and capacity. For the first time, we have attempted to define the relative contributions of the detrusor and mucosal layers to bladder compliance. Fetal bovine bladder compliance increases with fetal development. Elimination of the active component of smooth muscle tension improves compliance and increases capacity more than 60% in younger fetuses but only 35% in older fetuses. Active smooth muscle tension as evaluated by whole bladder cystometry is highest in the youngest fetuses and decreases with fetal age. Surgical removal of the detrusor layer (smooth muscle and connective tissue) also increases compliance and capacity substantially in all fetal bladders. These observations show that both smooth muscle and connective tissue are important in the function of the developing fetal bladder. Changes in both of these bladder wall components probably occur during development and are responsible for the physiologic changes observed.

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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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Comparative pharmacology of the male and female rabbit bladder neck and urethra: involvement of nitric oxide.

The present study compared the contractile and relaxant responses of male and female rabbit bladder neck and urethra to field stimulation (FS) and various contractile and relaxant agents, with special attention paid to the involvement of nitric oxide (NO) in the mediation of field-stimulated relaxation. FS at basal tension elicited a frequency-dependent contractile response in all preparations. The maximal response to high frequency FS was significantly greater in the bladder neck strips isolated from male rabbits than in those from female rabbits. There were no significant differences in the response to bethanechol or phenylephrine between strips isolated from males and females. Field-stimulated responses of the strips from male bladder neck and urethra were greater than the response to phenylephrine. The responses of all strips to FS were greater than those to bethanechol. In addition, the response to phenylephrine was generally greater than that to bethanechol. Phentolamine was a significantly more effective inhibitor of the response of the female bladder neck and urethral strips to FS than of the response of the male strips. The contractile response of all strips to phenylephrine was generally greater than that to bethanechol for both sexes and for both bladder neck and urethral strips. NG-nitro-L-arginine methylester (L-NAME) inhibited totally the field-stimulated relaxation of all strips. Isoproterenol stimulated a slowly developing but significant inhibition of phenylephrine prestimulated contractions. In conclusion, significant differences exist in the magnitude of field-stimulated relaxation between the bladder neck and urethra of both male and female rabbits, and, for all tissues, field-stimulated relaxation could be completely inhibited by pretreatment with L-NAME, an NO synthesis inhibitor.

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Pharmacological effect of ethanol on the function of rabbit corporal cavernosal tissue.

Pharmacologic and behavioral effects of alcohol on male sexual activity have long been controversial. Among the varied effects of alcohol, it has been described that ethanol reduces nitric oxide production. Appreciating the importance of nitric oxide-mediated regulation of corporal smooth muscle, this study was designed to investigate the in vitro pharmacologic effect of 1-5% ethanol on rabbit corpus cavernosum function. The results are summarized as follows. In isolated organ bath experiments, basal resting tension of corporal strips was significantly reduced with 3 and 5% ethanol exposure. Relaxation induced by field stimulation over a frequency range of 2-16 Hz was significantly decreased with 3 and 5% ethanol exposure. However, field-stimulated contraction at 32 Hz was reduced by 5% ethanol only. When corporal strips were preincubated with phenylephrine, 3 and 5% ethanol significantly inhibited field stimulated relaxation at all frequencies. Both phasic and tonic contraction induced by phenylephrine was significantly suppressed by 3 and 5% ethanol. KCl-induced contraction was decreased by 5% ethanol. ATP-induced relaxation was significantly enhanced by 1, 3 and 5% ethanol. Bethanechol-induced relaxation was significantly suppressed by 1, 3 and 5% ethanol. Direct nitroprusside-induced relaxation was not affected by any concentration of ethanol administration. These results demonstrated that ethanol had significant effects on both contraction and relaxation of rabbit corpus cavernosum. In general, corporal relaxation mediated through the acetylcholine-L-arginine-nitric oxide pathway was significantly more sensitive to ethanol than either ATP- or nitroprusside-induced relaxation.

Adenosine Triphosphate↗

What is the most accurate way to study the active properties of bladder smooth muscle?

There is often disagreement over the optimal method by which to study the active properties of smooth muscle. While some favor setting smooth muscle strips at a resting or passive tension of 1 g, others have argued in favor of determining the Lo or optimal length for maximal force generation for each individual strip. Setting each strip to its individual Lo is tedious, especially if one is dealing with multiple strips during one experiment. Is it possible to study smooth muscle strips at an average length at which most strips of similar dimensions exhibit their maximal force, and if this method is used to what extent does it underestimate the maximal force generated? When comparing bladder, smooth muscle strips 1 cm long from pregnant versus virginal rabbits, the average length at which maximal force was generated was 2.41 and 2.45 cm, respectively (p = n.s.). Studying all strips at a length of 2.5 cm (2.5 x the slack length) would have resulted in a 10% underestimate of the maximal force within each group (p = n.s.). We conclude that comparative bladder smooth muscle strip studies can be accurately carried out at an average fixed length provided that preliminary studies are done to determine the length-tension relationships for the specific experimental situation.

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Effect of partial outlet obstruction on the biphasic response to field stimulation at different concentrations of calcium.

The contractile response of the rabbit urinary bladder smooth muscle to field stimulation is biphasic in nature consisting of an initial phasic contraction followed by a prolonged tonic contraction. The phasic contraction is mediated by a rapid rise in intracellular free calcium concentration which in turn is achieved by a combination of the entry of extracellular calcium into the cell and by the mobilization and release of calcium from intracellular storage sites. Partial bladder outlet obstruction in rabbits is associated with a marked depression of contractile function. The current experiments were designed to: (1) investigate the role of extracellular calcium in mediating the phasic and tonic components of the contractile response to field stimulation and (2) determine the effect of partial outlet obstruction on this relationship. The results can be summarized as follows: in the control bladder, increasing the extracellular calcium concentration from 0.6 to 5.4 mmol/l enhanced the phasic contractile response to a 2-Hz stimulation to a significantly greater degree than the response to a 16-Hz stimulation. Increasing the extracellular calcium concentration had no effect on the plateau phase of the contractile response. Partial outlet obstruction significantly reduced the phasic and tonic responses to all frequencies of stimulation. In general, there was a greater reduction in the tonic response to field stimulation (relative to the phasic response).

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Effect of chronic ethanol consumption on the pharmacological response of the rabbit corpus cavernosum.

Previous studies demonstrated that acute in vitro exposure of corpus cavernosal tissue to ethanol decreased its response to field stimulation and pharmacological stimulation. In the current study the effects of chronic ethanol consumption on the responses of the rabbit corpus cavernosum to field stimulation and various autonomic agonists were investigated. Five percent (V/V) ethanol in drinking water was given to rabbits for 6 weeks. At the end of this time the in vitro response of the corpus cavernosum to various forms of stimulation was determined. The corporal smooth muscle taken from rabbits subjected to chronic ethanol consumption demonstrated the following characteristics compared to tissue taken from control rabbits. (1) Under basal conditions, both relaxation and contraction induced by field stimulation were significantly increased. (2) Contractions to both phenylephrine and KCl increased significantly. (3) In the tissue preincubated with phenylephrine, relaxations induced by field stimulation, ATP, and bethanechol were significantly enhanced. (4) The relaxation responses to sodium nitroprusside were not changed by chronic exposure to ethanol. These findings suggest that in vivo chronic ethanol administration augmented both stimulated contracation and stimulated relaxation of the corporal smooth muscle.

Alcoholism↗

Hyperplasia and apoptosis. Opposing cellular processes that regulate the response of the rabbit bladder to transient outlet obstruction.

BACKGROUND: Partial obstruction of the rabbit urethra induces rapid bladder growth. This growth is characterized by hypertrophy of smooth muscle cells in addition to hyperplasia of cells in the urothelium and serosa. The local synthesis of growth factors has been proposed to be influential in this growth since partial outlet obstruction rapidly increases the bladder's expression of basic fibroblast growth factor, while suppressing the expression of transforming growth factor-beta. Upon release of the outlet obstruction, the hypertrophied bladder regresses to its normal weight. Here, we examined whether regression of the hypertrophied rabbit bladder involves apoptosis (programmed cell death) of specific cellular elements and whether the expression of growth factors is altered concomitant with apoptotic cell deletion. EXPERIMENTAL DESIGN: Regressing rabbit bladders were analyzed for markers of apoptosis, including DNA fragmentation and histology. An in situ enzymatic immuno-histochemical procedure was utilized to localize apoptotic cells in these tissues. Finally, Northern blot analysis was used to identify changes in the expression of basic fibroblast growth factor and transforming growth factor-beta during bladder regression. RESULTS: Regressing rabbit bladders demonstrated the characteristic electrophoretic "ladder" pattern of DNA fragmentation associated with apoptosis. An in situ technique to distinguish cells with degraded nuclear DNA identified apoptosis only within the urothelium and serosal lamina of the regressing bladders. RNAs extracted from regressing bladders exhibited decreased expression of basic fibroblast growth factor mRNA as well as increased expression of transforming growth factor-beta 1 mRNA when compared with RNAs from hypertrophied bladders. CONCLUSIONS: We conclude that hyperplasia and apoptosis are opposing cellular processes that mediate the bladder's response to short-term obstructive stimuli and that local synthesis of growth-promoting and growth-inhibitory factors may be responsible for initiating both of these responses.

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