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PubMedDate not supplied

Sonographic evaluation of urinary bladder wall thickness in normal dogs.

Urinary bladder wall thickness was evaluated by ultrasonography in 16 normal dogs. Sterile saline solution was administered via urinary catheters to control the degree of bladder distention. Bladder wall thickness was measured on static ultrasound images in 4 locations and at 3 degrees of bladder distention (minimal, mild, and moderate). Four randomized distention sequences with 3 distentions per sequence were performed on each dog and the data were analyzed using Williams' balanced Latin square. Mean bladder wall thickness was 2.3 mm in minimally distended bladders (0.5 ml/kg saline), 1.6 mm in mildly distended bladders (2 ml/kg saline) and 1.4 mm in moderately distended bladders (4 ml/kg saline). Mean bladder wall thickness increased significantly with increasing body weight and with decreasing bladder distention. The caudoventral measurement location produced a statistically significant smaller measurement, with a difference of 0.3 mm. Sex did not affect bladder wall thickness. Distention sequence and repetition of distentions did not affect bladder wall thickness.

Anesthesia, Intravenous↗

PubMed1987

Rat urinary bladder denuded of urothelium. An in vivo model for the epithelial-stromal interactions in carcinogenesis.

To investigate epithelial-stromal interactions in bladder carcinogenesis, the authors developed an experimental model using a heterotopically transplanted rat urinary bladder (HTB). A rat urinary bladder which was completely denuded of epithelial cells ex vivo with hypotonic shock and a nonionic detergent was transplanted into a syngeneic recipient. No reepithelialization occurred during the 8-week posttransplant period. The basal lamina remained intact throughout this period and showed linear immunofluorescence with antibodies against laminin, Type IV collagen, and heparan sulfate-proteoglycan. When 1 X 10(5) to 5 X 10(5) dispersed normal urothelial cells were delivered into the HTB through an attached reservoir 4 days after transplantation, complete resurfacing by inoculated cells occurred within a few days. A transient hyperplasia was followed by a normal 2-3-cell-thick urothelial organization in 4 weeks. Cultured bladder carcinoma cells also resurfaced the denuded bladder basal lamina; the progressive growth of this neoplastic epithelium resulted in carcinoma in situ as well as foci of invasive carcinoma within 4 weeks following inoculation. This in vivo system has an advantage over other in vivo and in vitro models in that complete removal of epithelial cells can be achieved easily and completely; the course after reepithelialization can be modified by subsequent treatment, progression of neoplastic development can be closely observed by a change in the color of the aspirate, its cytology, and biochemical analysis of secretions; and an adequate amount of tissue can be available for subsequent examinations. The model is potentially useful not only for studying epithelial-stromal interactions during carcinogenesis, but also for examining the mechanisms of tumor invasion and metastasis.

Animals↗

PubMed2004

Paraganglioma of the urinary bladder: a lesion that may be misdiagnosed as urothelial carcinoma in transurethral resection specimens.

Paraganglioma of the urinary bladder is a rare tumor with characteristic histologic and immunohistochemical features. However, in our experience, it may be misdiagnosed as urothelial cancer because of 1) its frequent involvement of the muscularis propria; 2) morphology that may suggest urothelial cancer in transurethral resection specimens, particularly if there are artifactual changes induced by that procedure; 3) failure of pathologists to include it in their differential diagnosis when evaluating a bladder tumor; and 4) only a minority of the cases are associated with symptoms that might prompt consideration of the diagnosis. Distinction between paraganglioma and urothelial cancer is important because of likely different therapeutic options. In this report, we describe our experience with the histopathology of paragangliomas of the urinary bladder with emphasis on the histologic features that have led to their being misdiagnosed as conventional urothelial cancer and, most importantly, those that will help pathologists recognize this rare tumor of the bladder. Fifteen cases of paraganglioma of the urinary bladder were studied, 11 of them consult cases. They affected patients (8 male, 7 female) with a mean age of 49.5 years; only two had symptoms suggestive of the diagnosis, including hypertension during cystoscopy and episodic headache. Three consult cases were submitted with a diagnosis of "transitional cell carcinoma" and 4 with a diagnosis only of "bladder tumor." Histologically, "zellballen" and diffuse patterns were present in 12 (80%) and 3 (20%) of the cases. A delicate fibrovascular stroma was obvious in 14 (93%) cases. Other patterns included irregular nests and pseudorosette formation. Tumor necrosis, significant cautery artifact, and muscularis propria invasion were present in 1 (7%), 3 (20%) cases, and 10 (67%) cases, respectively. All 15 tumors were composed of large polygonal cells with abundant granular cytoplasm. Focal clear cells were present in 3 (20%). The nuclei were mostly uniform, although occasional pleomorphic nuclei were seen in 6 (40%) cases, and 2 (13%) had frequent pleomorphic nuclei. Mitoses were rare overall, and no abnormal mitotic figures were found. The major histologic features that led to misdiagnosis included a diffuse growth pattern, focal clear cells, necrosis, and muscularis propria invasion, with significant cautery artifact compounding the diagnostic problems. Immunohistochemically, 2 of 2 tumors were positive for neuron-specific enolase, 9 of 10 tumors for chromogranin, and 2 of 3 tumors for synaptophysin; 3 of 3 tumors were negative for cytokeratin and 1 of 1 tumor negative for HMB-45. Paraganglioma of the urinary bladder may be misdiagnosed as urothelial cancer, but a careful search for the characteristic histologic features and, if necessary, supportive immunohistochemical studies, should lead to a correct diagnosis.

Adolescent↗

PubMed1996

p53 mutations in transitional cell carcinomas of the urinary bladder in rats treated with N-butyl-N-(4-hydroxybutyl)-nitrosamine.

Involvement of p53 gene alterations has been demonstrated in a variety of human neoplasias including urinary bladder carcinomas. N-Butyl-N-(4-hydroxybutyl)nitrosamine (BBN)-induced urinary bladder carcinogenesis models in rodents have been widely used to study carcinogenic processes in this organ. In the present study, transitional cell carcinomas induced in the urinary bladders of male F344 rats treated with 0.05% BBN for 16 or 32 weeks and then sacrificed at experimental week 32 were analyzed for mutational changes in the p53 and H-ras genes by polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) analysis and subsequent DNA sequencing. The total p53 mutation incidences were 3/10 (30%) and 8/12 (66.7%) in rats treated with BBN for 16 weeks followed by 16 weeks' non-treatment, or in rats treated with BBN for 32 weeks, respectively, while the H-ras mutation incidences were 0/10 (0%), and 1/12 (8.3%), respectively. The present results indicate that mutations in the p53 gene might be involved in the process of urinary bladder carcinogenesis by BBN as part of a multistep pathway. However, considering the decreasing tendency in lesions with p53 mutations after stopping BBN administration, a p53 mutation alone would not appear to be sufficient to give a marked selective advantage to mutant cells. No evidence of H-ras mutation involvement was gained even for the late course of rat urinary bladder carcinogenesis.

Animals↗

PubMed1994

Pseudomalignant spindle cell proliferations of the urinary bladder.

Twelve cases of polypoid, nonrecurrent, pseudomalignant spindle cell proliferations of the urinary bladder (eight women and four men) were analyzed. Two patients had a simultaneous urinary bladder carcinoma. The lesions were characterized by proliferating spindle- or strap-shaped cells, which on electron microscopic examination (performed in all 12 cases) revealed characteristics of fibroblasts and myofibroblasts. The cells showed immunoreactivity for vimentin in all cases, for alpha-smooth muscle-specific and muscle-specific actin in six cases, for cytokeratins in five cases, and for CD 34 in one case. No immunoreactivity was observed for desmin, myoglobin, epithelial membrane antigen, S-100 protein, endothelial cell antigen (H and Y), CD 68, or factor VIII RAG. Immunoreactivity for Ki-67 and proliferating cell nuclear antigen was detected in up to 30% of the spindle cell nuclei. The static cytometric DNA analysis revealed a diploid, or in two cases a hyperdiploid, stem cell line. An awareness of this type of spindle cell lesion and its immunophenotypic characteristics and diversity is of importance to avoid an erroneous diagnosis of spindle cell sarcoma (in particular leiomyosarcoma and embryonal rhabdomyosarcoma) or spindle cell carcinoma.

Actins↗

PubMed1989

Neutral aminopeptidase: a potential marker enzyme of the amphibian urinary bladder epithelial cell apical membrane.

Antidiuretic hormone induces, in the apical plasma membrane of amphibian urinary bladder epithelial cells, the exocytotic insertion of intramembranous particle aggregates that probably contain water channels. Purification of the apical membrane is a way to characterize the aggregates. The isolation of such purified membranous fractions involves the use of specific exogenous or endogenous markers. One of them could be the neutral aminopeptidase (AP), whose activity was detected in urinary bladder. Enrichment in AP activity was observed in plasma membrane preparations compared to cell homogenates (X2.7). However, a large part of the enzyme activity was also recovered in the soluble fraction of the preparation, suggesting large proteolysis of the protein. The enzyme presents a low optimal pH (6.4) and a high specificity for proline-p-nitroanilide as compared to the AP present in kidneys and intestines. To localize the protein in the amphibian bladder epithelium, an immunological approach was necessary due to the low activity of the enzyme in this tissue. The low enzymatic activity also prevented the purification of sufficient amounts of the urinary bladder AP as antigen, and we prepared antibodies against purified AP from frog or toad kidneys where the activity is 60 times higher than in the bladder. The serum specificity was verified by spot immunodetection, Western blot, inhibition capacity of antibodies, and immunoadsorption on a solid support with the renal enzyme. The sera were found to be able to react with native as well as denatured forms of the kidney enzyme. Antibodies cross-reacted with several peptides of low molecular weight (40-60 kDa) from urinary bladder plasma membrane proteins (Western blot).(ABSTRACT TRUNCATED AT 250 WORDS)

Aminopeptidases↗

PubMed1995

Contractility of urinary bladder and vas deferens after sensory denervation by capsaicin treatment of newborn rats.

1. Capsaicin, a selective sensory neurotoxin, was given to newborn rats and at the age of 3 months the contractile activity of the urinary bladder detrusor muscle and vas deferens evoked by either electrical field stimulation (EFS) or exogenous adenosine 5'-triphosphate (ATP) and carbachol (urinary bladder), or ATP and noradrenaline (vas deferens) were tested. 2. EFS of the urinary bladder evoked contractions which consisted of cholinergic and purinergic components, since they could be partially blocked by either the muscarinic cholinoceptor antagonist, atropine (0.3 microM) or by desensitization of P2x-purinoceptors with alpha,beta-methylene ATP (10 microM). In capsaicin-treated rats, contractions of the urinary bladder evoked by EFS were significantly larger than those of control (vehicle-treated) animals, and this difference remained after the purinergic component of the contractions was blocked by desensitization of P2x-purinoceptors with alpha,beta-methylene ATP. However, when the cholinergic component of the contractions was blocked with atropine, the difference between the groups at 8 Hz and 16 Hz was abolished; EFS caused significantly larger contractions of the capsaicin-treated rat bladder only at frequencies of 2 Hz and 4 Hz. 3. EFS evoked contractions of the vas deferens consisted of adrenergic and purinergic components since they could be partially blocked by either the alpha-adrenoceptor antagonist, phentolamine (3 microM) or by alpha,beta-methylene ATP (10 microM). The contractions of the vas deferens were significantly larger than in the capsaicin-treated rats only at a frequency of 16 Hz. There were no differences between vas deferens contractions of the two groups either after desensitization of P2X-purinoceptors by alpha,beta-methylene ATP or in the presence of phentolamine.4. Contractions of the capsaicin-treated rat urinary bladder evoked by exogenous carbachol (0.1-100 microM) were not significantly different from those of controls, the pD2 values being 1.78 +/- 0.23 micro M and 1.90 +/- 0.20 micro M respectively. There was also no significant difference between the groups in contractions of the bladder evoked by ATP (10 micro M-3 mM).5. Contractions of the vas deferens evoked by either ATP (10 micro M-3 mM) or noradrenaline (1-1000 micro M) in the capsaicin-treated group showed no significant difference between control and capsaicin treated rats.6. In conclusion, the present results indicate that chronic capsaicin treatment increases the amplitude of contractions of the rat urinary bladder, an effect which preferentially involves the cholinergic component of the response; since the response to carbachol is unaffected, the change involves prejunctional mechanisms. In contrast, both the purinergic and adrenergic components of contraction in the vas deferens are unaffected by capsaicin. It is suggested that sensory nerves have a trophic influence on the development of parasympathetic nerves in the rat bladder; removal of sensory nerves shortly after birth results in an increase mainly in the cholinergic, and to a lesser extent purinergic component.

Adenosine Triphosphate↗

PubMed1992

Effect of acute distension on cholinergic innervation of the rat urinary bladder.

The effect of short-term urinary bladder distension on its cholinergic innervation was studied in Sprague-Dawley rats. Distension was induced for 3 h by forced diuresis and balloon outlet obstruction, and whole thick biopsy specimens were taken from the dome and lateral side of the anterior body 2, 7 and 21 days afterwards. The acetylcholinesterase (AChE) method was used to demonstrate the cholinergic nerves in the distended bladder wall. Cholinergic hypoinnervation was observed 7 days after the distension, persisting up to 21 days, although AChE-reactive nerves were then observed to be more numerous. The distribution of hypoinnervation was uneven, being more marked in the lateral side of the anterior body than in the dome. The distribution of AChE-reactive nerves varied even in the same biopsies, with areas of total hypoinnervation occurring next to areas of slightly diminished innervation. This was especially true 21 days after distension. The findings indicate transient damage to the cholinergic innervation, which may in turn explain the prolonged voiding difficulties often seen after catheterization of an overdistended bladder in a patient with urinary retention. The short-lasting effect of bladder dilatation therapy used to treat detrusor instability or interstitial cystitis may be due to the fairly rapid regeneration of cholinergic innervation.

Acetylcholinesterase↗

PubMed1999

Loss of heterozygosity in (LewisxF344)F1 rat urinary bladder tumors induced with N-butyl-N-(4-hydroxybutyl)nitrosamine followed by dimethylarsinic acid or sodium L-ascorbate.

Dimethylarsinic acid (DMA), a main metabolite of arsenicals which are carcinogenic in man, exerts tumor-promoting activity on rat urinary bladder carcinogenesis initiated with N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN). Sodium L-ascorbate (Na-AsA) is also a strong tumor promoter in this animal model. In this study, we used (LewisxF344)F, rats to compare molecular alterations in urinary bladder tumors caused by BBN followed by DMA or Na-AsA. Male, 6-week-old rats were given 0.05% BBN in their drinking water for 4 weeks, and then the rats in group 1 were maintained with no further treatment for 40 weeks. The animals of groups 2 and 3 were administered 0.01% DMA in their drinking water (group 2) or 5% Na-AsA in the powder diet (group 3) after the BBN treatment. Group 4 rats were given 0.05% BBN continuously for 36 weeks. At weeks 12, 20, 36 and 44, subgroups of rats were killed. Histopathological examination revealed promoting activity for DMA and, to a greater extent, Na-AsA on urinary bladder carcinogenesis. Loss of heterozygosity (LOH), detected with the polymerase chain reaction using 36 microsatellite markers, was found to be present in 2 of 9 (22%) urinary bladder tumors after treatment with DMA and 3 of 22 (14%) induced by continuous administration with BBN. No LOH was, however, detected in urinary bladder tumors after treatment with Na-AsA. The results thus suggest that the mechanisms of action of these two promoters, DMA and Na-AsA, may differ in rat urinary bladder carcinogenesis.

Animals↗

PubMed2006

Prognostic significance of homozygous deletions and multiple duplications at the CDKN2A (p16INK4a)/ARF (p14ARF) locus in urinary bladder cancer.

OBJECTIVE: The 9p21 locus is a major target in the pathogenesis of human urinary bladder cancer. This locus harbours the CDKN2A/ARF tumour suppressor gene, which encodes two cell-cycle regulatory proteins: p16INK4a and p14ARF. We studied how homozygous deletions and multiple duplications at this locus affect prognosis and survival in patients with bladder cancer. MATERIAL AND METHODS: Real-time quantitative polymerase chain reaction (QPCR), based on simultaneous amplification of ARF and a reference gene, glyceraldehyde-3-phosphate dehydrogenase, was used to measure homozygous deletions and multiple duplications in a population-based material consisting of 478 patients with urinary bladder cancer. Results from real-time QPCR were compared with clinico-pathological parameters and survival curves were generated using the Kaplan-Meier method. RESULTS: Real-time QPCR analysis showed 71 (15%) homozygous deletions and 8 (2%) multiple duplications. We were unable to find any association between either stage or grade and urinary neoplasms with homozygous deletions. However, although there were only a limited number of patients with multiple duplications, 7/8 of them had highly malignant tumours (G2b-G4 or > or = T1; p = 0.02). CONCLUSIONS: Urinary bladder cancers constitute a spectrum of neoplasms with varying clinical manifestations. We were unable to establish a prognostic relevance for patients with tumours harbouring homozygous deletions at the CDKN2A/ARF locus. However, our data did indicate that patients with multiple duplications at the CDKN2A/ARF locus had poor survival. This suggests that multiple duplications, in combination with other genetic changes, have cooperative effects which have a negative outcome on urinary bladder cancer prognosis.

Carcinoma, Transitional Cell↗

PubMed1995

Characterization and autoradiographic localization of [3H] alpha, beta-methylene adenosine 5'-triphosphate binding sites in human urinary bladder.

OBJECTIVES: To characterize [3H] alpha, beta-methylene adenosine 5'-triphosphate ([3H] alpha, beta-MeATP, a radioligand for P2x-purinoceptors) binding sites in the washed homogenates and membrane preparations of human urinary bladder and, using autoradiography, to localize [3H] alpha, beta-MeATP binding sites in human bladder. MATERIALS AND METHODS: Specimens were obtained from the fundus of the urinary bladder of male patients aged 56-79 years. The washed homogenates or membrane preparations of the bladder specimens were incubated with [3H] alpha, beta-MeATP and the bound and free radioligand separated by filtration. For autoradiography, cryostat sections were incubated with 10 nM [3H] alpha, beta-MeATP, washed, dried and exposed for 2 weeks to emulsion-coated coverslips. In both experiments, 100 microM beta, gamma-methylene ATP was used to determine non-specific binding. RESULTS: Six of 16 specimens in the binding assay and three of seven specimens in the localization study showed specific [3H] alpha, beta-MeATP binding. The binding process was saturable and the specific binding sites were composed of a high- and low-affinity component. The specific binding to membrane preparations was reduced in the presence of Mg2+ in the incubation medium. Competitive displacement experiments showed that the order of potency of the unlabelled ligands to displace the [3H] alpha, beta-MeATP binding was alpha, beta-methylene ATP > beta, gamma-methylene ATP > suramin > 2-methylthio ATP > ATP > ADP >> adenosine, which indicates that the binding sites are, or are linked to, P2x-purinoceptors. Autoradiography showed that the specific [3H] alpha, beta-MeATP binding sites were located only over the smooth muscle of the bladder. CONCLUSIONS: The results suggest that P2x-purinoceptors exist in human urinary bladder, although at a lower density than reported for rodent urinary bladder.

Adenosine Triphosphate↗

PubMed2004

Release of beta-nicotinamide adenine dinucleotide upon stimulation of postganglionic nerve terminals in blood vessels and urinary bladder.

Chemical signaling in autonomic neuromuscular transmission involves agents that function as neurotransmitters and/or neuromodulators. Using high performance liquid chromatography techniques with fluorescence and electrochemical detection we observed that, in addition to ATP and norepinephrine (NE), electrical field stimulation (EFS, 4-16 Hz, 0.1-0.3 ms, 15 V, 60-120 s) of isolated vascular and non-vascular preparations co-releases a previously unidentified compound with apparent nucleotide or nucleoside structure. Extensive screening of more than 25 nucleotides and nucleosides followed by detailed peak identification revealed that beta-nicotinamide adenine dinucleotide (beta-NAD) is released in tissue superfusates upon EFS of canine mesenteric artery (CMA), canine urinary bladder, and murine urinary bladder in the amounts of 7.1 +/- 0.7, 26.5 +/- 4.5, and 15.1 +/- 3.2 fmol/mg of tissue, respectively. Smaller amounts of the beta-NAD metabolites cyclic adenosine 5'-diphosphoribose (cADPR) and ADPR were also present in the superfusates collected during EFS of CMA (2.5 +/- 0.9 and 5.8 +/- 0.8 fmol/mg of tissue, respectively), canine urinary bladder (1.8 +/- 0.5 and 9.0 +/- 6.0 fmol/mg of tissue, respectively), and murine urinary bladder (1.4 +/- 0.1 and 6.2 +/- 2.4 fmol/mg of tissue, respectively). The three nucleotides were also detected in the samples collected before EFS (0.2-1.6 fmol/mg of tissue). Exogenous beta-NAD, cADPR, and ADPR (all 100 nm) reduced the release of NE in CMA at 16 Hz from 27.8 +/- 6.0 fmol/mg of tissue to 15.5 +/- 5.0, 12 +/- 3.0, and 10.0 +/- 4.0 fmol/mg of tissue, respectively. In conclusion, we detected constitutive and nerve-evoked overflow of beta-NAD, cADPR, and ADPR in vascular and non-vascular smooth muscles, beta-NAD being the prevailing compound. These substances modulate the release of NE, implicating novel nucleotide mechanisms of autonomic nervous system control of smooth muscle.

Acetaldehyde↗

PubMed1990

Inhibition of tumour development in the partially resected, proliferating rat urinary bladder.

Autoradiographic studies have shown that the urothelium of the rat urinary bladder is capable to considerably proliferate in response to a partial cystectomy (one-third resection of the bladder) as is indicated by a 190-fold increase of the 3H-thymidine labelling index above normal levels 45 h postoperatively and an enormous increase of the compartment of proliferating cells (so-called growth fraction). The stimulated urothelial proliferation can be synchronized by multiple, fractionated doses of hydroxyurea (HU), resulting in a high degree of synchrony. Based on these findings, the partial cystectomy model seemed to be a useful tool to examine whether stimulated proliferation exerts a modifying effect on initiation of urothelial carcinogenesis. Following feeding N-butyl-N-(4-hydroxybutyl)-nitrosamine by gavage in 3 fractionated doses during most pronounced proliferation 30, 45 and 70 h postoperatively, the development of bladder tumors proved to be significantly dose- and time-related inhibited. Accordingly, N-methyl-N-nitrosourea (MNU)-induced tumour formation was considerably reduced following intravesicular instillation of the carcinogen at a single dose 45 h postoperatively, when stimulated DNA synthesis reached its peak. Experiments testing a possible cell cycle specific dependence of MNU-initiated tumor development in the partially resected bladder after synchronization of the stimulated proliferation by HU revealed an inhibition of urothelial carcinogenesis in particular, when the carcinogen was administered during the early DNA synthesis phase. The mechanisms underlying the observed inhibition of tumor development in the regeneration urinary bladder are unknown. It is assumed that an increased capacity of the proliferating urothelial cells to repair carcinogen-induced DNA-damage may play an important role.

Animals↗

PubMed2005

Malignant pheochromocytoma of the urinary bladder.

A case of malignant pheochromocytoma of the urinary bladder is presented. A 54-year-old woman visited our hospital for screening and was found to have an abnormal mass in the bladder on ultrasonography. The patient was not hypertensive. Cystoscopy revealed a broad-based, small fingertip-sized, nonpapillary tumor on the posterior wall of the urinary bladder. Transurethral resection (TUR) was performed without suspicion of pheochromocytoma because of her well-controlled blood pressure and lack of characteristic symptoms. Transient elevation of systolic blood pressure to 240 mmHg occurred during resection of the tumor. Radical resection was therefore not possible. The serum norepinephrine level was elevated postoperatively. Pathologic examination revealed a malignant pheochromocytoma. On January 30, 2003, partial cystectomy of the residual tumor and pelvic lymphadenectomy were performed. She has had no clinical sign of recurrence for 1 year after the second operation.

Cystectomy↗

PubMed1999

Function of M3 muscarinic receptors in the rat urinary bladder following partial outlet obstruction.

PURPOSE: Partial outlet obstruction of the rat urinary bladder leads to hypertrophy and alteration in contractility of the detrusor muscle involving changes in muscarinic receptors. m3 muscarinic receptor subtype has been known to play a predominant role in contractility of normal urinary bladder. The purpose of the present study was to assess the role of m3 receptors in contractility of the obstructed bladder. MATERIALS AND METHODS: In male rats, partial outlet obstruction of the urinary bladder was performed by surgically tying a 6-0 suture around the bladder neck, reducing the diameter of it by 2/3 of the original size. Four weeks after the surgery, the bladders were removed and thin strips were microdissected. Similarly, bladder strips from age matched unoperated normal rats were obtained. Sets of four strips from four normal or four obstructed rats were mounted in an in vitro multi-muscle chamber containing normal physiological solution at 37C. The tension responses evoked by optimal electrical field stimulation at 1, 10, 30, 50, and 100 Hz, and the contracture responses evoked by 120 mM potassium and 0.01 to 300.0 microM carbachol were recorded using a Nicolet digital oscilloscope. Similar responses were recorded in different sets of four strips following exposure to 10 and 100 nM 4-DAMP, which is a muscarinic antagonist with a high affinity for m3 and m1 receptor subtypes. RESULTS: The obstructed bladders showed 119% increase in weight. In control physiological solution, the obstructed bladder strips did not show significant difference in electrically-evoked tension or carbachol contractures, but showed significantly lower potassium contractures compared with normal bladder strips. 4-DAMP at 10 to 100 nM significantly reduced the electrically evoked tension responses by about the same degree in normal and obstructed bladders, without affecting the potassium contractures. It significantly increased the EC50 values for carbachol contractures in normal bladder, and to a significantly lesser extent in obstructed bladder. Schild plots using the Hill transformed EC50 values showed that the pA2 value for 4-DAMP was not significantly different in normal and obstructed bladders. CONCLUSIONS: Significantly smaller potassium contracture in the obstructed bladder indicates that depolarizability of the detrusor muscle membrane, and consequently the activity of voltage-gated Ca2+ channels may be reduced in the detrusor after partial outlet obstruction. Lack of a significant difference in the effect of 4-DAMP on the electrically evoked tension responses and in the pA2 values for 4-DAMP assessed by carbachol contractures, in normal and obstructed bladder strips, indicates that m3 muscarinic receptors still play a predominant role in causing detrusor contractility in the obstructed bladder, as in the normal bladder.

Animals↗

PubMed1999

Evidence for beta3-adrenoceptor subtypes in relaxation of the human urinary bladder detrusor: analysis by molecular biological and pharmacological methods.

The purpose of the present study was to confirm the presence of beta3-adrenoceptor subtype in the relaxation of human urinary bladder detrusor tissue by reverse transcription-polymerase chain reaction (PCR); direct sequencing of the PCR product, in situ hybridization; and isometric contraction. Using reverse transcription-PCR, the mRNAs of three receptor subtypes (beta1, beta2, and beta3) were expressed in the human urinary bladder detrusor tissue. Direct sequencing of the PCR product of the above beta3-adrenoceptor revealed no mutation in the amplified regions. In situ hybridization with digoxygenin-labeled oligonucleotide probe revealed the presence of the mRNA of beta3-adrenoceptor subtype in the smooth muscle of the urinary bladder. The relaxant effects of isoproterenol (a nonselective beta-adrenoceptor agonist); ZD7114, BRL37344, and CGP12177A (putative selective beta3-adrenoceptor agonists); and SR59230A (a putative selective beta3-adrenoceptor antagonist) were tested using an isometric contraction technique. Isoproterenol in either the presence or absence of both atenolol (a beta1-adrenoceptor-selective antagonist) and butoxamine (a beta2-adrenoceptor-selective antagonist) revealed a relaxant effect on the carbachol-induced contraction of the human urinary bladder detrusor. Both BRL37344 and CGP12177A also revealed relaxant effects on the human urinary bladder detrusor, but ZD7114 did not elicit any relaxation. These results suggest that beta3-adrenoceptor may have some role in urine storage in the human urinary bladder.

Adrenergic beta-Agonists↗

PubMed1995

Sympathetic efferent activity in the viscerovascular reflexes induced by urinary bladder distension.

In chloralose-anesthetized cats, rapid distension of the urinary bladder with warm (37 degrees C) normal saline (50-60 ml) causes an increase in blood pressure and contraction of the spleen. This response is due to peripheral vasoconstriction. In this experiment, the evidence of direct involvement of the spleen, as well as splenic and splanchnic sympathetic efferent activity on the viscerovascular reflexes, was investigated by pharmacological and electrophysiological (single unit preparation) means and analysis. The viscerovascular reflexes induced by urinary bladder distension remained unaffected by propranolol, but phentolamine, guanethidine sulfate, and hexamethonium completely antagonized the reflex vasopressor response. All these results with these blocking agents show that sympathetic nerves are actively involved in the reflex responses to distension of the urinary bladder with activation at the postganglionic level involving alpha-adrenoceptors and thereby the release of catecholamines. It is thus evident that the same mechanisms operate in the case of reflex elevation of blood pressure and contraction of the spleen. After bilateral denervation of the splanchnic sympathetic nerves, bladder distension failed to produce a reflex response. The efferent activity from the splanchnic and splenic sympathetic nerves in producing a reflex rise in blood pressure was recorded for direct evidence. The significant increase of asynchronous spontaneous discharge rate in the splanchnic and splenic sympathetic nerves was found along with a rise in blood pressure during bladder distension. On the basis of this study, it may be suggested that the spleen as well as splenic and splanchnic sympathetic nerves play an important role in the control of viscerovascular reflexes.

Animals↗

PubMed2002

Distribution and changes with age of calcitonin gene-related peptide- and substance P-immunoreactive nerves of the rat urinary bladder and lumbosacral sensory neurons.

In the distal parts of the urinary tract, nerves containing calcitonin gene-related peptide (CGRP) or substance P (SP) are sensory with their cell bodies located in lumbosacral dorsal root ganglia. These two neuropeptides are recognised as being present in pelvic sensory nerves, and may be involved in the mediation of pain, stretch and/or vasodilatation. We have used indirect immunohistochemical techniques to examine the distribution and regional variation of nerves immunoreactive (-ir) for CGRP and SP in the urinary bladder and in neurons in lumbosacral dorsal root ganglia (L1-L2 & L6-S1) of young adult (3 months) and aged (24 months) male rats. Semi-quantitative estimations of nerve densities were made for CGRP-ir and SP-ir fibres innervating the dome, body and base of the urinary bladder. Quantitative studies were also used to examine the effects of age on the percentage of dorsal root ganglion neurons immunoreactive for CGRP and SP. There were very few immunoreactive axons in the dome and the overall density of innervation increased progressively towards the base of the bladder. The density of innervation in the aged rats revealed a slight reduction in CGRP and SP innervation of the detrusor muscle but was otherwise comparable to the young group. However, immunostaining of the lumbosacral dorsal root ganglia revealed that the percentage of CGRP- and SP-ir neuronal profiles showed a significant (P < 0.05) reduction from (mean +/- S.D) 44.5 +/- 2; 23.3 +/- 2 in young adult to 25.0 +/- 2.9; 14.8 +/- 1.6 in aged rats, respectively. These findings suggest that the involvement of CGRP and SP in urinary bladder innervation is relatively unchanged in old age, but their expression in dorsal root ganglion neurons is affected by age. The afferent micturition pathway from the pelvic region via these lumbosacral ganglia may be perturbed as a result.

Aging↗