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Biomedical subjects

R M Levin

Publications and source records attributed to R M Levin.

At least 181 records · Page 10Linked to original sources
PubMed1993

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.

Animals↗
PubMed1993

Response of isolated human neurogenic detrusor smooth muscle to intramural nerve stimulation.

The effect of intramural nerve stimulation of isolated strips of human detrusor was investigated and compared with the response of isolated detrusor strips of control bladders. All patients with neurogenic bladder underwent ileocystoplasty in order to resolve intractable incontinence and/or vesicoureteric reflux due to low compliance or severe detrusor uninhibited contractions. The response of isolated strips of neurogenic bladder to field stimulation was significantly greater than the response of isolated strips of control bladders. Tetrodotoxin virtually eliminated the response to field stimulation for both groups. Atropine (10(-6)M) almost completely inhibited the response of control bladder strips to field stimulation (4% of the response remaining), whereas the responses of the strips from neurogenic bladders were inhibited by approximately 70%. Low dose KCl (5 and 10 mM) significantly enhanced the detrusor contractility of control bladders, whereas the response of neurogenic bladders was unchanged. The responses of both groups were significantly inhibited in the presence of 20 mM KCl. The dose response curves and the ED50 values for KCl were similar for both neurogenic and control bladders. The rate of reduction of the response to field stimulation in the presence of zero calcium medium was significantly smaller for the isolated strips of neurogenic bladders than for the control bladders.

Adolescent↗
PubMed1993

Effect of thyroxine on urinary bladder autonomic receptor densities and contractility.

The effect of thyroxine on the response of urinary bladder strips to autonomic drugs and electrical stimulation was studied. Bladder strips from euthyroid, hyperthyroid and thyroidectomized rats were used. Rats were made hyperthyroid by intramuscular injection of thyroxine (250 micrograms/rat for 5 days). Surgical thyroidectomy was performed 12-15 weeks before the experiment. The contractile response of bladder strips from each of the 3 groups of rats to electrical field stimulation and the following drugs was measured: isoproterenol; bethanechol; methoxamine; adenosine triphosphate, and potassium chloride. Isoproterenol produced a significantly greater relaxation in strips from hyperthyroid than from euthyroid rats. The enhanced relaxation response to isoproterenol was accompanied by an increase in beta-adrenergic receptor density. The contractile response to methoxamine, adenosine triphosphate and potassium chloride was unchanged by pretreating the rats with thyroxine. The increase in contraction produced by bethanechol was the same in strips from hyperthyroid and euthyroid rats and the muscarinic receptor densities were also unaltered by thyroxine. Bladder strips from thyroidectomized rats showed the same response as strips from control animals following electrical field stimulation or exposure to isoproterenol, bethanechol, methoxamine, adenosine triphosphate and potassium chloride. These results demonstrate that thyroxine pretreatment enhances the relaxation of urinary bladder strips produced by isoproterenol and that this response is correlated with a hormone-induced increase in beta-adrenergic receptors in this tissue.

Animals↗
PubMed1993

The effect of terodiline on hyperreflexia (in vivo) and the in vitro response of isolated strips of rabbit bladder to field stimulation, bethanechol and KCL.

Hyperreflexia, a condition characterized by contractions of the urinary bladder, is not mediated by a micturition reflex. The contractions can be of neurogenic origin through spinal or supraspinal reflexes or of myogenic origin, independent of neuronal mediation. There is a clear relationship between hyperreflexia and symptoms such as urgency, frequency, nocturia and urinary incontinence. Therapies to reduce the presence of uninhibited bladder contractions include oral drug therapy, instillation drug therapy and parasympathetic nerve ablation. The current study characterizes the ability of terodiline to inhibit an experimental form of hyperreflexia and compares the efficacy and potency of terodiline and other agents on hyperreflexia and evoked contractions. The results can be summarized as follows: (1) terodiline inhibits the amplitude of the hyperreflexia at lower concentrations than it inhibits the frequency of hyperreflexia; (2) terodiline had no statistically significant effect on mean blood pressure at any concentration utilized; (3) terodiline had approximately the same potency for inhibition of 2 and 32 Hz stimulation for both the bladder body and base; (4) terodiline inhibited the maximum contractile response to bethanechol and also shifted the curve to the right, demonstrating that terodiline is a mixed inhibitor, and (5) terodiline was a noncompetitive inhibitor of KCl.

Animals↗
PubMed1993

Correlation of contractile function of the rabbit corpus cavernosum with NADH fluorescence.

The NADH/NAD ratio is a measure of potential metabolic energy in smooth muscle tissue. Previous studies on bladder smooth muscle demonstrated that during active contraction when energy utilization is high, NADH is rapidly oxidized to NAD resulting in a decrease in the ratio of NADH/NAD. Intracellular systems utilizing ATP as an energy source are characterized by changes in the NADH/NAD ratio. This ratio can be monitored simultaneously with changes in smooth muscle tissue tone using an optical fiber probe which continually monitors NADH fluorescence and contractile activity of the same smooth muscle preparation. The present study correlates alterations in the ratio of NADH/NAD with both spontaneous and induced contractions and relaxations in the rabbit corpora cavernosa. The results show a high degree of correlation between a decrease in spontaneous fluorescence (decrease in the NADH/NAD ratio) and spontaneous contraction. An increase in tension was followed in time by a decrease in the NADH/NAD ratio. This was consistent for all strips showing significant spontaneous activity. ATP caused a rapid decrease in tension which was correlated with a decrease in fluorescence. The relative decrease in NADH fluorescence was proportional to the relative decrease in tension. Under basal conditions (0.8 g passive tension) ATP and nitroprusside stimulated a marked reduction in tension, but only ATP stimulated a substantial decrease in NADH fluorescence. Bethanechol and isoproterenol relaxed the corporal tissue to a relatively small degree which correlated with relatively small decreases in fluorescence. Methoxamine stimulated a substantial contraction of corporal smooth muscle which correlated with a rapid and significant decrease in NADH fluorescence.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Effect of ryanodine on the contractile response of the normal and hypertrophied rabbit urinary bladder to field stimulation.

Bladder contraction, similar to most smooth muscle contraction, is dependent on both the translocation of extracellular calcium across the cell membrane, and the calcium-stimulated release of intracellular bound calcium. Partial outlet obstruction of the urinary bladder induces a marked increase in bladder mass which results in part from a substantial hypertrophy of the smooth muscle elements. In addition, the increase in bladder mass is associated with specific contractile dysfunctions. It is not known if the contractile dysfunction induced by partial outlet obstruction is related to alterations in calcium metabolism. Ryanodine is a pharmacological tool which can be utilized to study the role of intracellular calcium in mediating contractile events. Ryanodine stimulates the loss of intracellular calcium (bound in the sarcoplasmic reticulum) and reduces the participation of intracellular calcium in the contractile response to specific forms of stimulation. The current study investigates the effect of partial outlet obstruction on the ryanodine inhibition of the contractile response of rabbit urinary bladder to field stimulation. New Zealand White rabbits were anesthetized and catheterized with an 8-french Foley catheter. A 00 silk suture was surgically placed around the catheterized urethra, the incision closed, and the catheter removed. After 1, 3, 5 and 7 days of partial outlet obstruction, the bladder was rapidly removed and utilized immediately for contractile studies. The effect of ryanodine (0-80 microM) on the peak response to 2-, 8- and 16-Hz field stimulation at 0.6, 1.8 and 5.4 mM calcium was determined.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Effects of purines on rabbit corpus cavernosum contractile activity.

At least three well documented neuropharmacologic mediators participate in physiologic erection: inhibition or cessation of alpha-adrenergic transmission, increases in both cholinergic (acetylcholine) and non-adrenergic non-cholinergic (NANC) transmission. In-vitro studies of rabbit corporal smooth muscle reveal that adenosine tri-phosphate (ATP) has a variable effect on muscle tension depending on the level of basal tone. ATP has a pronounced relaxant effect on corporal smooth muscle at either high basal tension or pre-stimulated tension. ATP stimulates a contraction in corporal smooth muscle at low tension. The current studies compare the effects of a series of purines (adenine, adenosine, AMP, ADP, ATP and beta-gamma methylene ATP) on both basal tension and on field-stimulated relaxation. The results demonstrate that all purines relax both baseline tension (2g) and phenylephrine-stimulated contraction. Following phenylephrine pre-stimulation: beta-gamma methylene ATP was significantly more potent than ATP at inhibiting tension. ADP, AMP, adenosine, and adenine produced intermediate dose-response relaxation curves. At 2 grams baseline tension, adenosine, ADP, and AMP were equally potent relaxing agents, ATP was slightly less potent. Adenine and beta-gamma-methylene ATP induced similar dose-response curves which were significantly less potent and efficacious than adenosine, AMP, ADP, and ATP. Field stimulation of phenylephrine pre-contracted tissue strips produce relaxation at both low and high frequencies. None of the purines either facilitated or inhibited the corporal response to field stimulation. We conclude that field stimulated relaxation of rabbit corporal smooth muscle is independent of purinergic relaxation.

Animals↗
PubMed1993

Osteoporosis: prevention is key to management.

Osteoporosis is a leading cause of morbidity and mortality in elderly women. The key to managing osteoporosis is to recognize that it may be more easily prevented than treated. Preventive measures focus on increasing the peak bone mass reached in all individuals by age 20 by counseling younger patients on lifestyle habits and dietary measures that affect bone growth, and on slowing the rapid age-related bone loss that occurs in postmenopausal women with the use of estrogen replacement therapy. In addition to its effects on bone, estrogen therapy also alleviates the signs and symptoms of menopause and possibly reduces the risk of death due to cardiovascular disease. A relationship between estrogens and breast cancer remains controversial, but a recent meta-analysis suggests no increased risk of this malignancy among women who receive hormone replacement therapy.

Adult↗
PubMed1992

Effect of outlet obstruction on pyruvate metabolism of the rabbit urinary bladder.

Bladder function is dependent upon cellular metabolism of substrates and the adequate generation of high-energy phosphate compounds. Partial outlet obstruction induces a marked decrease in bladder function which is associated with a significant decrease in the oxidative metabolism of glucose. The current investigation was designed to determine whether the time course of the decrease in mitochondrial oxidation in the hypertrophied urinary bladder is similar to the time course of the contractile dysfunction observed. In these studies we determined: 1) the rate of 14C-pyruvate metabolism to 14CO2 in control and obstructed tissue (1, 3, 5 and 7 days), and 2) the mitochondrial enzymatic activities of malate dehydrogenase and citrate synthase. The results can be summarized as follows: 1) The rate of pyruvate metabolism decreases by over 50% within one day following partial outlet obstruction, and remains at this level for the seven day period of study. 2) Kinetic analysis demonstrates that the change in enzymatic activity is related to a decrease in Vmax; the Kd for pyruvate is similar for control and after all time periods of obstruction. 3) The enzymatic activity of malate dehydrogenase and citrate synthase is reduced by over 50% within one day following partial obstruction, and remains at this level throughout the 7 day study period. These metabolic results correlate in time and duration with the decreased ability of the bladder to empty following partial outlet obstruction.

Animals↗
PubMed1992

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↗
PubMed1992

Effect of outlet obstruction on 3H-thymidine uptake: a biochemical and radioautographic study.

Experimental outlet obstruction in the rabbit is characterized by a rapid and substantial increase in urinary bladder mass. Although it is clear that both the smooth muscle and connective tissue compartments are increasing in mass, there is little information on the mechanisms by which this increase in mass occurs. As an initial investigation in this process, urinary bladders from normal and obstructed NZW rabbits were exposed in vitro to tritiated thymidine (3H-TdR) in order to determine which populations of cells are induced to synthesize DNA following outlet obstruction, and when, after obstruction, such synthesis occurs. Biochemical analysis of nucleic acids was performed on each specimen to determine total and radioactive DNA. These analyses showed a marked increase in DNA synthesis at 24 hours following obstruction which remained relatively high through seven days after obstruction. There was a decline in labelling at 14 days. Incorporation of radioactive label peaked at three days and declined to control levels by 14 days. Samples of tissue were taken from each subject and processed for radioautography. At 24 hours after obstruction, significant numbers of cells of the basal cell layer of the urothelium are observed to be actively involved in DNA synthesis, while the other two tissue compartments (muscularis and connective tissue) show no significant changes when compared to normal specimens. Connective tissue, on the other hand, showed significantly increased levels of labelling above control level from three to 14 days after obstruction. Smooth muscle cells were observed to be frequently labelled in only one of the experimental bladders observed three days after obstruction.

Animals↗
PubMed1992

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.

Animals↗
PubMed1992

Comparative autonomic responses of the cat and rabbit bladder and urethra.

The cat and the rabbit have both been utilized extensively in the study of lower urinary tract function. Previous studies have demonstrated that although both the cat and rabbit bladder are approximately the same weight, the in-vitro cat bladder can generate over 6 times the intravesical pressure of the rabbit bladder. The current study was designed to compare the ability of the isolated bladder to generate pressure with the pressures required to maintain flow through the isolated urethra for both the cat and the rabbit. The results can be summarized as follows. 1) The cat bladder is visibly much thicker than the rabbit bladder, and in vitro cystometry demonstrates that it is far less compliant than the rabbit bladder. 2) Over 20 cm.H2O pressure is required to begin flow through the isolated cat urethra preparation, whereas 5 cm.H2O begins flow through the rabbit urethra. 3) Increasing the flow rate (up to 7-fold) through both the isolated cat and rabbit urethra increases intraurethral pressure only slightly. 4) Both the isolated cat and rabbit urethra respond strongly to field stimulation and alpha-adrenergic stimulation (relative to the opening pressure required to begin flow), but not to cholinergic stimulation. 5) Field stimulation following pre-stimulation by methoxamine induces a strong relaxation of the pre-stimulated cat urethra, but an additive contraction in the pre-stimulated rabbit urethra. These studies demonstrate that in order for the cat to empty its bladder, it must generate a comparatively high intravesical pressure, whereas the rabbit is required to generate a relatively low intravesical pressure.

Animals↗
PubMed1992

Is lamina propria matrix responsible for normal bladder compliance?

Immunohistochemistry using monoclonal and polyclonal antibodies to extracellular matrix proteins is a highly sensitive tool for the characterization of matrix components. For the first time in the normal and noncompliant human bladder we have used antibodies to collagen types I, III and IV, and elastin to provide morphological correlation with mechanical properties noted clinically. In the normal bladder elastin and collagen types I and III showed intense localization in the lamina propria with modest localization in the detrusor layer. In contrast, lamina propria staining in the noncompliant bladder was essentially unchanged, while there was intense localization within the detrusor layer. Significantly, this intense localization consisted of collagen type III and elastin with little increase in type I. Type IV collagen is associated with basement membranes and individual smooth muscle cells, and shows commensurate increase in specimens with muscle hypertrophy and/or hyperplasia. These observations suggest that in the normal bladder the lamina propria may be a major structural capacitance layer with the smooth muscle covering it. The collagen fibers of the lamina propria may gradually unfold during filling, thus, accounting for normal compliance while in the noncompliant bladder the capacitance layer shifts outward to the infiltrated smooth muscle, thus, preventing the normal expansion of the lamina propria. The smooth muscle infiltration consists of a deposition of collagen type III and elastin with little increase of collagen type I, and it results in a loss of compliance. The pattern of localization would suggest that the smooth muscle is responsible for this accumulation.

Adolescent↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

Effects of acute in vitro overdistension of the rabbit urinary bladder on DNA synthesis.

Urinary bladder outflow obstruction induces a myriad of structural and functional changes in the organ. Among the morphological responses to outlet obstruction is both hyperplasia and hypertrophy of specific cellular elements. The initial event which has been implicated in the initiation of the response to outflow obstruction is an initial period of high intravesical pressure and subsequent distention of the bladder. In a previous study, it was shown that at one day following partial outlet obstruction there was a marked increase in thymidine labelling of the urothelium, at 3-5 days, the labeling shifted from the urothelium to the interstitial and serosal elements. The current study was designed to determine if acute distention of the urinary bladder can induce an increase in DNA synthesis (3H-thymidine incorporation), and localize the increased DNA synthesis via autoradiography of 3H-thymidine. In this study, the bladders of adult male New Zealand white rabbits were mounted in isolated in vitro baths. Each control bladder was filled to either 5 or 20 ml. with saline, or distended to 120% of capacity. The bladders were incubated for 7 hours at which time 3H-thymidine was placed both within and outside the bladder for an additional one hour. At the end of the time the bladder was divided at the ureteral orifices into bladder body and base, and each body and base divided into two sections. One section of bladder body and base was quantitatively analyzed for both labelled and unlabelled DNA; the second section was fixed and prepared for autoradiography. The results can be summarized as follows: 1) Acute overdistention for 8 hours induced a slight decrease in the DNA concentration which was mediated by edema of the bladder wall. 2) Acute overdistention induced a 5-fold increase in 3H-thymidine incorporation in the bladder body and a 3-fold increase in the bladder base. Radioautoradiography of the overdistended bladders showed significant and substantial labelling which was confined to the urothelial basal cells. The control bladders showed little or no labelling. These results are consistent with the theory that acute distention following partial outlet obstruction initiates the proliferative response of the bladder to outlet obstruction, and the urothelium is the initial target of the proliferative response. Functionally, the proliferative response may serve to maintain the structural as well as functional integrity of the bladder.

Animals↗