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R M Levin

Publications and source records attributed to R M Levin.

At least 199 records · Page 11Linked to original sources
PubMed1992

Urinary bladder function in the tight-skin mouse.

Tight-skin mice develop hypertrophy of connective tissue and tendons, associated with increases in collagen concentration in skin, heart, lungs, and tail. The bladders from these mice have not previously been examined. Because of the purported importance of collagen in bladder wall structure and compliance, we examined collagen content, micturition characteristics, and length-tension relationships in bladders from tight-skin mice. Bladder collagen content and concentration were approximately 70% greater in 5-6 month tight-skin mice than age-matched controls, but bladder mass, protein content, and protein concentration were similar. Tight-skin mice urinated larger volumes more frequently during the light cycle, and the functional bladder capacity appeared to be greater than that of controls. There was a small shift to the right of the passive length-tension curves of bladder strips from tight-skin mice, but the shift was not statistically significant. The magnitude of active tension development was the same. The data suggest that bladder collagen concentration does not necessarily determine bladder capacity or compliance. It is suggested that other factors, such as the ratio of collagen subtypes or the collagen:elastin ratio may have more importance for the maintenance of bladder distension.

Animals↗
PubMed1992

Comparison of urinary bladder function in 6 and 24 month male and female rats.

Micturition characteristics, collagen composition, and in vitro urinary bladder strip contractility were examined in young adult (six month) and old (24 month) male and female Fischer 344 rats. Although young female rats consumed significantly less water than young males, there were no differences in volumes of urine excreted. Old females excreted significantly more urine than old males, but there were no differences in volumes of water consumed. Old male rats had similar micturition frequencies during the light and dark cycles, in contrast to females and young males, where the number of micturitions during the dark cycle was significantly greater than those during the light cycle. The mean and maximal micturition volumes were significantly greater in old males compared to young males and old females during both the light and dark cycles. Bladders from female rats weighed significantly less than bladders from males of the same age, and the bladders from young rats weighed less than those of old rats. The protein and collagen concentrations were significantly less in bladder bodies from young females than old females. The amount of collagen resistant to digestion by Pronase, and thus thought to be cross-linked, was significantly greater in bladders from old rats compared to young. No differences between groups were found in the contractile responses of bladder base strips. There were trends for the absolute contractile responses of bladder body strips from old males to field stimulation, carbachol, ATP, and KCl to be larger than the other groups, and for strips from the young females to be smaller. The responses of strips from young females to field stimulation and KCl were significantly less than those of young males or old females, and responses to 10(-3) M ATP were less than those of old females. Responses of strips from old males to 60 mM KCl were significantly greater than those of young males. The differences in contractility could be attributed to the differences in strip mass. It appears, therefore, that urinary bladder function in male and female rats is unaffected by increasing age between 6 and 24 months.

Adenosine Triphosphate↗
PubMed1992

Effect of tetrodotoxin on the phasic and tonic responses of isolated rabbit urinary bladder smooth muscle to field stimulation.

The response of the rabbit urinary bladder to field stimulation (80 volts, 2-32 Hz, 1 msec duration) is biphasic, consisting of an initial phasic contraction mediated by cholinergic and purinergic neurotransmitters, followed by a prolonged tonic contraction which is solely cholinergic. Obstructive hypertrophy of the bladder induces a variety of contractile alterations including a significantly greater reduction in the tonic component of the contractile response as compared to the phasic component. This results in a severe dysfunction in the ability of the bladder to empty. One possibility is that the inability of the bladder to maintain tension and empty efficiently may be related to a degeneration of nerves innervating the bladder smooth muscle. In addition to the well documented neuropathy, the bladder undergoes hypertrophy +/- hyperplasia of both smooth muscle and interstitial cellular elements, alterations in the metabolism of substrates, alterations in the synthesis of structural and smooth muscle proteins, and alterations in the deposition of collagen. The purpose of this study was to 1) to create a specific neuropathy in the absence of the additional structural, smooth muscle, and metabolic changes that are induced by partial outlet obstruction; and 2) determine if the contractile dysfunctions induced by the neuropathy have properties similar to the contractile dysfunctions induced by outlet obstruction. In the present study, a progressive "smooth muscle neuropathy" was induced in isolated strips of male rabbit urinary bladder smooth muscle by incubating isolated strips of urinary bladder body in the presence of increasing concentrations of tetrodotoxin (15-1500 nM). In these studies, we determined the effect of increasing concentrations of tetrodotoxin (TTX) on the response to field stimulation utilizing 2 Hz and 32 Hz, at 80 V and 1 ms duration. The effects of TTX on maximum rate of contraction, peak contraction and tonic contraction were monitored. In addition, the effects of atropine (cholinergic muscarinic blockage) and ATP-desensitization (purinergic inhibition) on the effects of TTX were also determined. The results can be summarized as follows: 1) Both atropine and ATP desensitization individually inhibited significantly the peak response to field stimulation. 2) Atropine abolished the tonic response. 3) TTX inhibited the tonic contraction at significantly lower concentrations than it inhibited peak contraction. Thus, at low concentrations of TTX, a condition similar to that seen in obstructive hypertrophy was created. 4) The ED50 in the presence of atropine was significantly greater than the ED50 following ATP desensitization. This may indicate that there are separate synaptic elements for cholinergic and purinergic transmission.(ABSTRACT TRUNCATED AT 400 WORDS)

Adenosine Triphosphate↗
PubMed1992

Effects of sensitization on the permeability of urothelium in guinea pig urinary bladder.

Permeability of the guinea pig urinary bladder was investigated in a model of experimental cystitis induced by intravesical antigen challenge following sensitization. Guinea pigs were sensitized by intraperitoneal injections of ovalbumin (10 mg./kg.) given on days 1, 3, and 5. The studies described were done four weeks after the last injection. Controls (injected with saline) were used at the same time as sensitized animals. Each group (control and sensitized), was divided into two subgroups; guinea pigs challenged with intravesical ovalbumin (10 mg./ml., one ml.) and those receiving one ml. saline intravesically. Immediately following the antigen (or saline) challenge, one ml. of 14C-urea urea was placed into the bladder for two hours. We examined the peripheral blood concentrations of 14C-urea at periods of time up to 120 minutes. There was a progressive increase in the blood level of 14C-urea with time only in the sensitized group challenged with antigen (ovalbumin). There was no 14C-urea present in the blood of the sensitized group without antigen challenge, or in either unsensitized group. We also measured isotope concentration in the bladders and found a significantly higher concentration of isotope in the bladders from ovalbumin-treated sensitized guinea pigs. We believe that this animal model of cystitis is an improvement over previous models because of its physiological relevance. In this model, cystitis is produced without mechanical or chemical damage to the bladder mucosa. A discussion of the model in relation to interstitial cystitis is presented.

Animals↗
PubMed1992

Effect of partial obstruction of the rabbit urinary bladder on malate dehydrogenase and citrate synthase activity.

Previous studies have demonstrated that partial outlet obstruction in rabbits induced a significant decrease in oxidative metabolism in urinary bladder smooth muscle. The current experiments were designed to determine whether the decreased oxidative metabolism of obstructed bladder tissue is associated with alterations in the activities of specific mitochondrial enzymes. The activities of two important enzymes in the tricarboxylic acid cycle, malate dehydrogenase and citrate synthase, were measured in samples of bladder body and base from normal bladders and in bladders from rabbits in which partial outlet obstruction had been produced seven days prior to the experiments. The results can be summarized as follows: malate dehydrogenase activity was similar in bladder body and base isolated from control rabbits; and decreased by approximately 40% in both segments of the bladder isolated from obstructed rabbits. In contrast to malate dehydrogenase, citrate synthase activity was significantly higher in the bladder body than in the base of normal rabbits. Outlet obstruction caused about a 50% decrease in activity of this enzyme in the bladder body, but had no significant effect on citrate synthase activity of the bladder base. These findings demonstrate that the deficiency in bladder function following partial outlet obstruction is associated with a marked decrease in the activities of two essential enzymes in oxidative metabolism: malate dehydrogenase and citrate synthase. This decrease in enzyme activity is consistent with the previously observed decrease in oxidative metabolism and would be expected to lead to an inability of the tissue to supply sufficient metabolic energy for proper contractile function.

Animals↗
PubMed1992

Effects of anoxia on the biphasic response of isolated strips of rabbit bladder to field stimulation, bethanechol, methoxamine and KCl.

The contractile response of the bladder can be divided into two phases: an initial rapid increase in tension and a prolonged period of sustained tension (plateau phase). The bladder empties primarily during the plateau phase of the contractile response. These two phases can be differentiated using both pharmacologic and metabolic agents, indicating that the two phases have independent energy requirements. The present study compares the phasic (peak) and tonic (plateau) components of the responses of isolated strips of bladder body and base to field stimulation, bethanechol, methoxamine and KCl administration. New Zealand White rabbits were anesthetized with pentobarbital, and the bladder was removed. The bladder was divided between body and base at the level of the ureteral orifices. Three strips of bladder body and three strips of bladder base were mounted in separate baths containing Tyrode's solution at 37 degrees C and equilibrated with 95% O2, 5% CO2. Anoxia was produced by changing the gas mixture to 95% nitrogen, 5% CO2. The effects of anoxia on the responses to field stimulation, bethanechol, methoxamine and KCl were determined at different times after the initiation of anoxia. The results of these studies can be summarized as follows: (1) Anoxia induced time-dependent plateau phases of the response to field stimulation (2 and 32 Hz). (2) The rate of inhibition of the plateau phase was significantly and substantially greater than that of the peak phase in both the bladder body and base. (3) Similarly, anoxia inhibited the plateau phase of the bladder body's response to bethanechol to a significantly and substantially greater degree than anoxia inhibited the peak contraction.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Effect of pinacidil on spontaneous and evoked contractile activity.

Uninhibited bladder contractions have been associated with a variety of bladder dysfunctions including outlet obstruction, neurogenic bladder, incontinence, and other neurologic and nonneurogenic bladder disorders. One class of compounds that is gaining popularity and support for the treatment of hyperreflexia is potassium channel openers, such as pinacidil and cromakalim. In general, these agents act by hyperpolarizing the smooth muscle membrane, resulting in an increase in membrane stability which in turn would be expected to inhibit spontaneous and evoked contraction. It is the purpose of this study to compare the potency and selectivity of pinacidil at inhibiting both hyperreflexia in vivo, and several forms of in vitro contractile stimulation in the rabbit. The following is a summary of the results. (1) Pinacidil is an effective inhibitor of hyperreflexia in the in vivo rabbit model. (2) Pinacidil is a substantially more potent inhibitor of the amplitude of the hyperreflexia than the frequency. (3) Pinacidil was substantially more potent at inhibiting the contractile response to 2-Hz stimulation than to 32-Hz stimulation, but was equally effective at inhibiting field stimulation of the bladder base and body. (4) Pinacidil was significantly more potent at inhibiting the peak response to field stimulation than the rate of tension generation. (5) Pinacidil was equally potent and effective at inhibiting the phasic and tonic components of the response to field stimulation. (6) Pinacidil was a more potent inhibitor of methoxamine stimulation of the bladder base than bethanechol stimulation of the bladder body. (7) Pinacidil was a noncompetitive or mixed inhibitor of both methoxamine and bethanechol stimulation, whereas it was a competitive inhibitor of KCl stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Influence of the bathing medium on the contractile responses of the rabbit urinary bladder.

This study examined contractile responses of the in vitro rabbit whole-bladder preparation to field stimulation, bethanechol and KCl in Tyrode's solution and minimum essential medium (MEM). We found frequency-dependent increases in intravesical pressure in bladders incubated in Tyrode's solution and MEM. However, bladders incubated in MEM consistently responded with greater increases in intravesical pressure compared to those incubated in Tyrode's solution. Similarly, there were frequency-dependent increases in the rate of pressure generation in bladders incubated in Tyrode's solution and MEM, and bladders incubated in MEM responded with greater rates of pressure generation than those incubated in Tyrode's solution at frequencies of 1, 2 and 4 Hz. In addition, there were significant increases in intravesical pressure generated in response to administration of 500 mmol/l bethanechol and 186.4 mmol/l KCl in bladders incubated in MEM compared to Tyrode's solution but no changes in the rate of pressure generation. The influence of L-methionine, one of the constituents of MEM, on the responses of whole bladders to nerve stimulation was also investigated. L-methionine at concentrations of 0.1 and 1.0 mmol/l had no effects on the increase in intravesical pressure or rate of pressure generation following nerve stimulation. It is speculated that the increases in contractile responsiveness of bladders incubated in MEM are related to the combination of amino acids, vitamins and other constituents of the cell culture medium.

Animals↗
PubMed1992

Effect of ryanodine on mitochondrial respiration.

Ryanodine is a pharmacological agent that stimulates calcium leakage into the cytoplasm resulting in an increase in tension. In skeletal muscle, ryanodine acts primarily on the sarcoplasmic reticulum whereas in smooth muscle, the sites of action are less clear. Visually, the increase in tension is slow and the time course can be mimicked by mitochondrial poisoning and the resultant leak of mitochondrial calcium into the cytoplasm. Although it has been reported that ryanodine has no effect on calcium flow into or from mitochondria, the effect of ryanodine on mitochondrial oxidative function was not studied. In the current investigation direct measurements of the effect of ryanodine on mitochondrial oxygen utilization were made. The results demonstrate that ryanodine, even at high concentrations, has no effect (stimulatory or inhibitory) on mitochondrial oxidation.

Animals↗
PubMed1992

Correlations of purinergic, cholinergic and adrenergic functions in rabbit corporal cavernosal tissue.

Erection involves cholinergic, adrenergic as well as non-cholinergic non-adrenergic nerves. Endothelial-derived relaxation factor plays an important role in mediating smooth muscle relaxation, which is crucial in initiating and maintaining erection. We previously showed that adenosine 5'-triphosphate (ATP) can induce significant relaxation in rabbit corporal cavernosal tissue. The present study presents effects of different neurotransmitters and the role of endothelium in controlling the contractile/relaxant status of rabbit cavernosal tissue. These studies utilized isolated tissue strips prepared from the corpus cavernosum of sexually mature male New Zealand white rabbits. The results can be summarized as follows: (1) field stimulation caused relaxations with rebound contractions in most strips; (2) bethanechol (250 microM), isoproterenol (20 microM) and ATP (1 mM) all induced relaxations, though the relaxation induced by bethanechol was poorly sustained; (3) removal of the endothelium by rubbing decreased the relaxation to field stimulation and virtually eliminated the relaxation induced by bethanechol, but had no effect on the relaxation responses to isoproterenol and ATP; (4) methoxamine (200 microM) stimulated a sustained contraction of corporal cavernosal tissue, an effect unaltered by rubbing the strips; (5) low dose epinephrine induced relaxation, whereas higher concentrations contracted the tissue, and (6) beta-adrenergic inhibition with propranolol (20 microM) was significantly more effective than mascarinic blockade with atropine (20 microM) in eliminating relaxation caused by field stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Smooth muscle myosin isoform distribution and myosin ATPase in hypertrophied urinary bladder.

Hypertrophy of the urinary bladder was produced in rabbit by partial ligation of the urethra. Electrophoresis of the bladder smooth muscle myosin on highly porous (3.5-7% gradient) SDS-polyacrylamide gel revealed two heavy chain isoforms, SM-1 and SM-2 with approximate molecular weights of 204,000 and 200,000, respectively. The ratio of the SM-2 to SM-1 heavy chain is 3:1 for myosin isolated from normal bladder smooth muscle, and this ratio changes to about 1:1 in hypertrophied bladder. Despite a change in the ratio of SM-2 to SM-1, the myosin ATPase and the actin-activated ATPase activities are not altered in response to hypertrophy.

Animals↗
PubMed1991

Creatine kinase activity in normal and hypertrophied rabbit urinary bladder tissue (following partial outlet obstruction).

The urinary bladder depends on intracellular ATP to support a number of essential intracellular processes including contraction. The concentration of ATP is maintained by mitochondrial oxidative phosphorylation, cytosolic glycolysis and the cytosolic activity of creatine kinase, the enzyme that catalysis the rapid transfer of a phosphate from creatine phosphate (CP) to ADP resulting in the formation of ATP. Prior studies in this lab and others have demonstrated that mitochondrial respiration is significantly lower in hypertrophied bladder tissue (induced by partial outlet obstruction of the white New Zealand Rabbit). In addition to decreased mitochondrial respiration, there are significant increases in glycolysis and lactic acid formation in the hypertrophied tissue. In view of the increased glycolysis and decreased mitochondrial function in the hypertrophied tissue, and the importance in creatine kinase in maintaining cytosolic levels of ATP, the current study was designed to determine if outlet obstruction induces any changes in the activity of creatine kinase. The following is a summary of the results: 1) The bladder mass increased from 2.2 +/- 0.2 gm to 11.5 +/- 1.6 gm at 7 days following outlet obstruction. 2) The intracellular concentrations of both ATP and CP were significantly reduced in the bladder tissue following 7 days of obstruction. 3) The percent of protein (per tissue mass) was significantly lower in the obstructed bladders, although the percent of soluble protein was similar. 4) Creatine kinase activity of control bladders showed linear kinetics with a Vmax = 1120 nmoles/mg protein/4 min and Km = 147 microM CP.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗
PubMed1991

The prevention of osteoporosis.

Osteoporosis is the most common metabolic bone disorder in the United States. The spine is frequently involved, so that elderly women with kyphosis due to multiple compression fractures ("dowager's hump") are commonly seen in a geriatric practice. However, the most serious manifestations of osteoporosis is hip fracture. Whereas vertebral crush fractures are painful and cause spinal deformity, hip fractures cause significant morbidity and mortality. Some 250,000 hip fractures occur each year in the United States, with a mortality of 12% to 20%. For those who survive the acute event, nearly half have their life-style dramatically changed. Many become chair-bound. Some need to enter nursing homes. Many become so despondent that they lose their will to live. The direct and indirect cost of caring for these patients is +7 billion to +12 billion a year. In the absence of adequate treatment of established osteoporosis, prevention takes on heightened importance. Several strategies require consideration, from dietary measures to hormonal treatments to the newest possibility, bisphosphonate therapy.

Aged↗
PubMed1991

The ability of insulin treatment to reverse or prevent the changes in urinary bladder function caused by streptozotocin-induced diabetes mellitus.

1. The effects of insulin treatment on in vivo and in vitro urinary bladder function in streptozotocin-diabetic rats were investigated. 2. Diabetes of 2 months duration resulted in decreases in body weight and increases in fluid consumption, urine volume, frequency of micturition, and average volume per micturition; effects which were prevented by insulin treatment. 3. Insulin treatment also prevented the increases in contractile responses of bladder body strips from diabetic rats to nerve stimulation, ATP, and bethanechol. 4. Diabetes of 4 months duration also resulted in decreases in body weight, and increases in fluid consumption, urine volume, frequency of micturition, and average volume per micturition, effects which were reversed by insulin treatment for the final 2 months of the study. 5. Insulin treatment reversed the increases in contractile responses of bladder body strips from diabetic rats to nerve stimulation, ATP, and bethanechol. 6. The data indicate that the effects of streptozotocin-induced diabetes on urinary bladder function are both prevented and reversed by insulin treatment.

Animals↗
PubMed1991

Effect of lithotripsy on immature rabbit bone and kidney development.

Although extracorporeal shock waves have been used to treat kidney stones for several years, little is known to their effect on developing tissue. In order to determine if lithotripsy has any negative effects on development, immature rabbits were used to study the relationship of extracorporeal shock waves to renal and skeletal growth. Rabbits in both the control and treatment groups had metallic clips placed surgically to demarcate the kidneys. Following unilateral kidney and femoral head treatment of the respective study groups with the Dornier Lithotripter Model HM-3, the rabbits were allowed to grow to maturity (six months). Plain radiographs were taken at three months. There was no significant difference between control and study groups when length of the kidneys or femurs, the diameter of the femoral heads, or the rabbits weights were compared. At six months of age, the rabbits were weighed, then sacrificed. The kidneys and femurs were removed. Comparisons between the control and study groups were then made for weight of the rabbit, weight and volume of the individual kidneys, femoral length, and femoral head diameter. Following these measurements sectioning and histologic examinations were done. In all parameters grossly and histologically, there was no statistically significant difference. It is concluded from this study that treatment with extracorporeal shock waves does not adversely affect overt rabbit renal or bone growth, making treatment of pediatric patients with ESWL appear safe in regard to these parameters. Future studies will be directed at confirming these findings in children.

Animals↗
PubMed1991

Effects of sensitization on female guinea pig urinary bladder function: in vivo and in vitro studies.

Although bladder inflammation is known clinically to produce a variety of symptoms including urgency, frequency, and pain, there are only a few experimental studies that directly relate bladder inflammation with urodynamic and functional alterations. We have used the sensitized guinea pig model to study the effects of inflammation on micturition parameters, cystometry, and in vitro bladder contractility. This model depends on the allergic response of the bladder mucosa to ovalbumin, an otherwise non-irritative agent, as an antigen. In vivo exposure of the bladder to ovalbumin via urethral catheterization induced a prompt and marked increase in the number of micturitions in antigen-sensitized guinea pigs. Ovalbumin had no effects on the micturition parameters in the control group. Using in vivo cystometry, intravesical exposure to ovalbumin induced a significant decrease in both the pressure at which micturition was induced, and the volume at which micturition was induced. Ovalbumin had no effect on cystometric parameters of the control animals. In vitro exposure of whole-bladder preparations to ovalbumin induced a significant contractile response only in the bladders isolated from the sensitized guinea pigs. The responses of the isolated bladders to field stimulation and bethanechol were identical for bladders from both sensitized and control animals. In conclusion, exposure of the bladder to ovalbumin in the sensitized animal induced an increase in the frequency of micturitions and a decrease in the pressure and volume at which micturition was induced. Thus, intravesical exposure of the bladder mucosa to a substance that the bladder has been sensitized to can induce alterations in micturition that are consistent with the clinical symptoms of "urgency and frequency".

Animals↗