Biomedical subjects

R M Levin

Publications and source records attributed to R M Levin.

At least 163 records · Page 9Linked to original sources

PubMed1993

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)

Animals↗

PubMed1993

Expression of constitutive heat shock protein-70 in normal (non-stressed) rabbit urinary bladder tissue.

The expression of constitutive HSP-70 in the urinary bladder was determined by SDS-PAGE and western blotting using a mouse monoclonal antibody against HSP-70. The western blot analysis showed that the mouse anti-HSP-70 cross-reacted with a 70 kDa protein present in the extracts of the urinary bladder muscle and mucosa. Densitometric scanning of the western blots allowed us to specifically quantitate the relative amounts of the HSP-70. The quantitation of the HSP-70 by combining immunoblotting and densitometry using a laser scanner is reproducible and this technique requires only a small amount of tissue. The amounts of HSP-70 can be estimated from a standard curve of nanogram(ng) of HSP-70 vs absorption from the immunoblots. The amounts of HSP-70 in the muscular and mucosal layers in the body of the urinary bladder are more than those in the base of the bladder. The presence of HSP-70 in the muscle and mucosal epithelium of the bladder was demonstrated by immunohistochemical analysis of freshly removed tissue from the base and the body of bladder from normal animals.

Animals↗

PubMed1993

Urothelial permeability of the isolated whole bladder.

The urothelium of the bladder presents an effective barrier to the penetration of solutes from the urine into the bladder wall. Previously, we have demonstrated that the dye indigocarmine can be utilized intravesically to study urothelial permeability. In general, intravesical indigocarmine (administered in vivo) will not penetrate the bladder wall unless the urothelium is damaged by overdistension, acetone administration, or mechanical damage. Unfortunately, using in vivo methodologies, one is limited in the study of the effect of specific conditions and permeations on bladder permeability. In the current study an isolated in vitro whole bladder model was developed to quantitatively study the permeability of the bladder urothelium. In these studies, the penetration of indigocarmine into and through the bladder wall was quantitated under various conditions. The in vitro bladder was filled by infusing 1% indigocarmine in saline in a step-wise manner at the rate of 10 ml in 10 minutes followed by a stabilization period of 10 minutes. Samples were taken from the bath at 20 minutes intervals for spectrophotometrical analysis of the dye. At the end of experiment the bladder was washed in saline for 10 minutes, and stored and extracted in formalin. In general, no indigocarmine penetrated the urothelium until the in vitro capacity was reached and exceeded. At intravesical volumes greater than capacity, the dye concentration in the bath increased very rapidly, even though the integrity of the bladder wall remained intact. In bladders treated with a gentle 50% acetone wash for 1 minute the dye started to penetrate into the bath at intravesical volumes of 25% of capacity and increased rapidly thereafter.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetone↗

PubMed1993

Age-related changes in the response of the rat urinary bladder to neurotransmitters.

The effect of age on the contractile response of the rat urinary bladder to various neurotransmitters was studied using in vitro detrusor strips isolated from female Wistar rats. The contractile responses to 8 neurotransmitters were determined for rat urinary bladders isolated from 3 age groups: 24, 16, and 6 months old. The results can be summarized as follows: 1) There was no age-dependent change in the maximum response to KCl. 2) The contractile response to norepinephrine, adenosine 5'-triphosphate (ATP), and serotonin increased with age. 3) The relaxation response to isoproterenol was significantly less in 24-month-old rats than in the other 2 age groups. 4) There were no age related changes in the responses to acetylcholine, prostaglandin F2 alpha, and angiotensin II. 5) Vasoactive intestinal polypeptide (VIP) failed to induce any response in the rat bladders of any group. 6) There were no significant differences in the ED50s for the 5 neurotransmitters among the 3 age groups. In summary, significant differences in the response to adrenergic, purinergic, and serotonergic stimulation were found as a function of age, whereas no age related changes in the response to cholinergic or generalized depolarization with KCl were found.

Aging↗

PubMed1993

Effect of partial outlet obstruction on choline acetyltransferase activity in the rat and rabbit.

Partial outlet obstruction of the rabbit bladder induces a rapid and significant increase in bladder mass. This increase in mass is associated with a variety of specific contractile dysfunctions, characterized by a marked decrease in the response to field stimulation (acting through the release of neurogenic transmitters). There is histological evidence indicating that the decrease in the contractile response of isolated strips of rabbit urinary bladder to field stimulation is associated with a degeneration of synaptic membranes within the bladder detrusor (neuropathy). In the current experiments, the effect of partial outlet obstruction in rabbit and rat urinary bladders on choline acetyltransferase activity (ChAT) were determined and correlated with both the level of bladder hypertrophy (increase in mass) and the contractile response to field stimulation. The results can be summarized as follows: In the rabbit, partial outlet obstruction induced a rapid 5-fold increase in bladder mass over the 7 day period of study. This increase in mass was associated with a decrease in the contractile response of isolated strips of bladder body and base to field stimulation and a decrease in ChAT activity. Interestingly, the rabbit bladder base showed a significantly higher ChAT activity than the bladder body, although the contractile response to muscarinic stimulation was significantly greater in the bladder body than in the base. In the rat, partial outlet obstruction induced a mild 2-fold increase in bladder mass.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1993

Effect of partial urinary outlet obstruction in the rabbit on the incorporation of adenine into adenine nucleotides in bladder smooth muscle.

Bladder outlet obstruction induces marked morphological, functional, and metabolic changes within the urinary bladder. Recent studies indicate that there is a close correlation between the contractile dysfunction induced by partial outlet obstruction and a marked decrease in mitochondrial oxidative activity of the hypertrophied bladder tissue. The current study investigates the effect of partial outlet obstruction on adenine metabolism within the bladder tissue. After transport into the cell, adenine becomes available as a substrate for adenine phosphoribosyl transferase (APRT), the enzyme that catalyses the non-mitochondrial conversion of adenine into AMP. Subsequently, AMP is phosphorylated to ADP, the phosphate acceptor in mitochondrial oxidative phosphorylation. The results of these studies demonstrate that partial outlet obstruction induces a significant increase in 14C-adenine uptake into the urinary bladder smooth muscle which in turn provides substrate for APRT and results in an increase in 14C-AMP synthesis. In contrast, the rate of incorporation of adenine into ATP+ADP was similar for both control and obstructed tissue. The activity of APRT was not significantly different in control and obstructed tissue.

Adenine↗

PubMed1993

Effect of partial outlet obstruction on contractility: comparison between severe and mild obstruction.

Detrusor dysfunction is one of the most common problems in patients with outflow obstruction secondary to benign prostatic hyperplasia. These patients complain of various symptoms, including urinary frequency, urge incontinence, difficulty in voiding, and retention. The severity of the symptoms is dependent on the stage of disease and/or severity of the obstruction. We compared the changes in the rat detrusor function following both mild and severe models of partial outlet obstruction in the rat. Outflow obstructions were created by ligation of the urethra over which a catheter was placed. The size of the catheter determined whether the severity of obstruction was mild or severe (1.70 mm for mild obstruction and 1.09 mm for severe obstruction). Changes in the bladder weight, length-tension relationships, and the contractile response to field stimulation, pharmacologic agonists, and KCl were studied in bladders isolated from 1 and 2 week obstructed rats. Bladder weights of all obstructed rats increased significantly. The weight of the severe obstructed rats were significantly greater than rats subjected to mild obstruction. In general, passive length-tension curves of obstructed rats were shifted to right. The magnitude of the active tension induced by high KCl was higher in the mild obstruction and lower in the severe obstruction. The maximum response to KCl of mild obstruction was generated at greater lengths than for the other groups. In general, the contractile responses of the mild obstructed bladder body to field stimulation, bethanechol, KCl, and ATP, and of the bladder base to field stimulation, KCl, and methoxamine, were significantly increased when compared to the responses of the control bladder body and base. However in the severe obstructed bladder, the responses to field stimulation, KCl, ATP, and methoxamine were significantly reduced from the responses of the control strips; the response to bethanechol was similar for control and the severe obstructed groups. In conclusion, the severity of outlet obstruction significantly altered the contractile response of the bladder. Mild obstruction induced a mild increase in bladder mass, which was associated with significant increases to all forms of stimulation. Severe outflow obstruction induced a substantial increase in bladder mass and a significantly greater reduction in the response to field stimulation than the response to bethanechol (which was unchanged).

Adenosine Triphosphate↗

PubMed1993

Distribution and function of the adrenergic and cholinergic receptors in the fetal calf bladder during mid-gestational age.

Previous studies on the developing fetal bovine bladder demonstrate that compliance is low during early stages of fetal development and increases with fetal age. In addition, the pharmacological response of isolated fetal bovine bladder smooth muscle strips to field stimulation and bethanechol increased in proportion with the gestational age. In the adult bladder (rabbit), the contractile response to autonomic receptor stimulation and the autonomic receptor density showed a parallel gradation in the the bladder between bladder dome and the urethra. The present studies were designed to determine the distribution of the cholinergic and adrenergic receptors in the urinary bladder of the fetal calf at mid-gestational age, and to correlate the receptor density with the magnitude of the response to receptor stimulation. Each bladder body was separated into upper, middle, and lower segments. For the functional studies, circular and longitudinal strips were cut from each bladder segment and stimulated with field stimulation (FS), bethanechol, methoxamine, isoproterenol, and KCl. Autonomic receptor assays were performed using 3H-QNB (muscarinic cholinergic), 3H-DHE (alpha adrenergic), and 3H-DHA (beta adrenergic) as ligands. In general, there were no significant differences in receptor density among the three bladder segments. However, the density of muscarinic receptors was significantly greater than the density of alpha- or beta-adrenergic receptors for all bladder segments. The receptor densities correlated very well with the functional response of isolated bladder strips to the specific autonomic agonists. The contractile response of isolated bladder strips to the specific autonomic agonists. The contractile responses of the strips to FS, bethanechol, and methoxamine were not significantly different among the three different bladder segments.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1993

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↗

PubMed1993

Effects of pregnancy on urethral and bladder neck function.

Pregnancy and menopause induce morphologic as well as functional changes in the female urethra. Symptoms of bladder irritation (frequency, urgency) and incontinence are frequent findings in these conditions and are considered to be due to alterations in the distribution of autonomic receptors induced by the changes in the hormonal milieu. In the present study, the functional responses to field stimulation (FS) and autonomic agonists of the bladder neck and urethra of pregnant, and virgin New Zealand White rabbits were compared using isolated muscle strips. Passive length-tension studies demonstrated a significantly greater compliance of strips (bladder neck and urethra) from pregnant rabbits than from virgin rabbits. FS elicited frequency dependent contractile responses in all strips. Phentolamine was significantly more effective at inhibiting the field stimulated contractile response of urethral strips from pregnant than from virgin rabbits. Atropine was significantly more effective at inhibiting the response to FS of strips isolated from bladder necks of virgin rabbits than in strips isolated from pregnant rabbits. Atropine was significantly less effective at inhibiting the response to FS of strips isolated from urethras of pregnant rabbits than of strips from virgin rabbits. Strips of bladder neck and urethra isolated from virgin rabbits responded with significantly greater contraction to phenylephrine than strips isolated from pregnant rabbits. The magnitude of field stimulated relaxation was significantly greater in urethral strips than in bladder neck strips, and also greater in urethral strips isolated from virgin rabbits than in strips isolated from pregnant rabbits. In conclusion, pregnancy induces profound hormonal changes which, in turn, result in the alteration of the compliance and functional responses of the bladder neck and urethra to various forms of autonomic stimulation and relaxation.

Analysis of Variance↗

PubMed1993

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.

Animals↗

PubMed1993

The effect of caffeine on the contractile response of the rabbit urinary bladder to field stimulation.

1. Smooth muscle contraction is mediated by an increase in the concentration of cytoplasmic free calcium. 2. Low concentrations of caffeine can induce transient contraction of smooth muscle through the release of intracellular calcium from intracellular storage sites. 3. The current study determined the effect of caffeine (0.4-100 microM) on the response of the in vitro whole bladder preparation to field stimulation (FS) at 0.6, 1.8, and 5.4 mM extracellular calcium. 4. The following parameters were determined: basal pressure (BP), peak pressure response (PP), maximal rate of pressure generation (PR), maximal rate of bladder emptying (RE), and percent of volume emptied (VE). 5. The results demonstrated that in the absence of caffeine, BP, PP, and PR were increased progressively as a function of both frequency of stimulation and the concentration of calcium. 6. In addition, caffeine significantly increased the rate of pressure generation at 0.6 and 1.8 mm calcium.

Animals↗

PubMed1993

Role of calcium in mediating the biphasic contraction of the rabbit urinary bladder.

1. The response of the urinary bladder to field stimulation is biphasic in nature consisting of an initial phasic contraction followed by a prolonged tonic phase which lasts for the duration of the stimulation. 2. The phasic response is mediated by the release of neurohumoral transmitters, primarily acetylcholine (via muscarinic receptor stimulation) and ATP (via purinergic receptor stimulation). The tonic component is mediated entirely via muscarinic receptor stimulation. 3. The present study investigates the dependence on extracellular calcium of the phasic and tonic contractile responses to field stimulation, bethanechol, and ATP. The results can be summarized as follows: 4. Field stimulation (2 and 32 Hz) and bethanechol evoke a biphasic contractile response whereas ATP evokes only a phasic response. 5. There were no significant effects of either calcium channel blockers or calcium fee EGTA medium on either spontaneous contraction or basal tension of muscle strips. 6. The calcium channel antagonists diltiazem and verapamil inhibited both the phasic and tonic responses induced by field stimulation (both 2 and 32 Hz) in a dose dependent manner. 7. For both 2 and 32 Hz stimulation, the ED50 s for the inhibition of the tonic phases of the responses to field stimulation were significantly lower than the ED50s for the inhibition of the phasic responses. 8. The tonic phase of the responses to field stimulation were inhibited to a significantly greater degree than the phasic responses by incubation in calcium-free medium containing EGTA. 9. Both the phasic and tonic components of the response to bethanechol stimulation were inhibited equally, and followed a similar time course as the tonic component of field stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗

PubMed1993

Effect of partial outlet obstruction of the rat urinary bladder on the response to alterations in the concentrations of potassium and calcium.

1. The contractile response of the 7 day obstructed bladder to field stimulation was significantly increased from that of the control bladder. 2. In the presence of 1.8 mM calcium (normal Tyrode's solution) the contractile response of control bladders to low-frequency field stimulation was significantly enhanced by increasing the potassium concentration from 2.5 to 7.5 or 12.5 mM. 3. Increasing the potassium concentration had no effect on the response of the obstructed bladder to low-frequency field stimulation. 4. Increasing the extracellular calcium concentration enhanced detrusor contractility in a dose-dependent manner in both control and obstructed bladders. 5. The magnitude of the effect of increasing the extracellular calcium concentration were greater in the obstructed bladder than in the control bladder. 6. These results suggest that calcium transporting mechanisms of the cell membrane and intracellular calcium storage and mobilization may be significantly affected by partial outflow obstruction.

Animals↗

PubMed1993

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↗

PubMed1993

Developmental aspects of bladder contractile function: evidence for an intracellular calcium pool.

Recent studies indicate that specific functional changes in smooth muscle accompany development and that these functional differences may relate to developmental alterations in intracellular calcium content. The possibility that neonatal bladder smooth muscle might be more permeable to calcium ions was tested using the radioligand H3 PN-200 and subsequent Scatchard analyses. No differences in either receptor density or the dissociation constants were noted in comparisons between neonatal and mature rabbit bladder smooth muscle. The sensitivity to calcium in isolated bladder smooth muscle strips exposed to high potassium was tested following calcium depletion. Calcium repletion was performed and dose response curves were generated, which showed that the neonatal strips had a significantly lower effective dose producing 50% of maximal response than their mature counterparts (1.5 versus 7.5 mM., p < 0.05). These findings are consistent with the hypothesis that intracellular binding and secondary calcium release are low in neonatal bladder smooth muscle, and that they increase with maturation. These studies are also consistent with the studies showing maturational increases in the intracellular binding and storage of calcium (sarcoplasmic reticulum), which have been reported in the developing rabbit and sheep myocardium.

Animals↗

PubMed1993

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↗

PubMed1993

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.

Animals↗