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Stephen A Zderic

Publications and source records attributed to Stephen A Zderic.

At least 19 recordsLinked to original sources

Smooth muscle trans-membrane sarcoglycan complex in partial bladder outlet obstruction.

The urinary bladder experiences both distension and contraction as a part of the normal filling and emptying cycle. To empty properly, tension generated intracellularly in a smooth muscle cell must be smoothly and efficiently transferred across its sarcolemma to the basement membrane, which mediates its binding to both the extracellular matrix and to other cells. As a consequence of urethral obstruction, the bladder cannot generate appropriate force to contract the organ, thereby leading to inefficient emptying and associated sequelae. In this study, an animal model of urethral obstruction was utilized to study the membrane-associated structures that transfer tension across the sarcolemma of bladder smooth muscle cells. Immunohistochemical localization of key components of the smooth muscle tension transfer apparatus (TTA) was performed utilizing specific antibodies against:(1) the alpha-chains of type IV collagen, a basement membrane component, and (2) beta-sarcoglycan, an integral membrane protein that is a participant in the physical linkage between the cytoskeleton and the basement membrane. We demonstrate, in obstructed animals, that there is a pronounced disruption of the TTA with a physical displacement of these two components that can be demonstrated at the level of the light microscope using scanning confocal microscopy. Electron microscopy further demonstrates significant increases in the size of the junctional plaques between smooth muscle cells.

Animals↗

Altered expression of thin filament-associated proteins in hypertrophied urinary bladder smooth muscle.

AIMS: Obstruction of the urinary bladder outlet induces detrusor smooth muscle (DSM) hypertrophy. The goal of this study was to determine whether the composition of thin filament-associated proteins, known to play important roles in cytoskeletal structure and/or the regulation of contraction, is altered in DSM during hypertrophy. METHODS: DSM hypertrophy was induced in male rabbits by partial ligation of the urethra. Sham-operated rabbits served as a control. Reverse transcriptase-polymerase chain reaction (RT-PCR) and real-time PCR revealed a significant increase in the expression of mRNAs for basic (h1) calponin (CaP), and alpha-isoform of tropomyosin (Tm) in hypertrophied DSM compared to controls. Western blotting and two-dimensional (2-D) gel electrophoresis showed enhanced expression of these proteins and also a significant increase in the expression of beta-non muscle and gamma-smooth muscle actin in the DSM from obstructed bladders, while alpha-actin remained constant. RESULTS: Enhanced expression of these proteins in the DSM from obstructed bladders was confirmed by immunofluorescence microscopy. Double immunostaining with Cap/Tm and alpha/beta-actin-specific antibodies showed co-localization of these proteins in myocytes. Colocalization of smooth muscle specific myosin and CaP to cytoplasmic filaments in cells dissociated from the hypertrophied DSM indicated that these cells are differentiated smooth muscle cells. CONCLUSIONS: The change in the isoforms of actin, Cap, and Tm may be part of the molecular mechanism for bladder compensation in increased urethral resistance.

Actins↗

Activation of the calcineurin pathway is associated with detrusor decompensation: a potential therapeutic target.

PURPOSE: We hypothesized that the calcineurin pathway mediated some of the complex remodeling process that allows a bladder subjected to partial outlet obstruction to adapt to its new workload. Atrial natriuretic factor mRNA expression served as a marker of calcineurin activation. MATERIALS AND METHODS: A total of 16 New Zealand White rabbits underwent surgical creation of partial outlet obstruction, followed by randomization to receive cyclosporin A (20 mg/kg intramuscularly twice daily) or no additional treatment for 14 days. Three animals underwent 2 weeks of partial bladder outlet obstruction followed by bladder biopsy and the reversal of obstruction. RESULTS: Atrial natriuretic factor expression was seen only in bladders with severe hypertrophy and it disappeared with the reversal of outlet obstruction. Cyclosporin A treatment resulted in a decrease in atrial natriuretic factor mRNA expression (p <0.05) and a marked shift in myosin heavy chain A-to-B ratios toward normal (p <0.01) and an increase in smooth muscle cross sectional area (p <0.05). Bladder mass decreased 40% but did not attain statistical significance (p = 0.08). CONCLUSIONS: The calcineurin pathway has a significant role in bladder wall hypertrophy following partial outlet obstruction. Bladder hypertrophy could not be fully prevented by cyclosporin A, suggesting that multiple signaling pathways are involved in this pathophysiology. The expression of myosin heavy chain AB isoforms is regulated in part by the calcineurin pathway.

Animals↗

Partial bladder outlet obstruction induces urethral smooth muscle hypertrophy and decreased force generation.

PURPOSE: PBOO leads to increased urinary frequency, decreased void volume, hypertrophy of the detrusor SM, and alterations in contractile and regulatory proteins. This study was done to determine whether PBOO induced increases in urinary frequency and detrusor SM hypertrophy are associated with an alteration in the contractility and expression of myosin isoforms in urethral SM. MATERIALS AND METHODS: PBOO was surgically induced in male New Zealand White rabbits, and sham operated rabbits served as controls. After surgery, rabbits were kept 12 days, and prior to sacrifice, urine output and voiding frequency were monitored by keeping the animals in metabolic cages for 24 hours. Animals with increased urinary frequency (mean +/- SEM 43 +/- 12 voids per 24 hours) and sham operated rabbits (6 +/- 3 voids per 24 hours) were used for this study. Morphology of the urethra was studied using light and immunofluorescence microscopy. The expression of myosin isoforms was analyzed at the mRNA and protein levels by RT-PCR and Western blotting. RESULTS: The urethral wall and SM of PBOO rabbits showed hypertrophy. The force produced by the longitudinal muscle strips of PBOO animals in response to phenylephrine, KCl, or electrical field stimulation was decreased 50%, 37% and 40%, respectively. Immunofluorescence microscopy revealed a decrease in nerve density. RT-PCR and Western blotting showed a decrease in the expression of myosin isoform SM-B with a concomitant increase in SM-A at the mRNA and protein levels. CONCLUSIONS: Our data show hypertrophy of the urethral wall and SM, and alterations in contraction, innervation, and myosin isoforms in PBOO induced detrusor hypertrophy.

Animals↗

Increased corpus cavernosum smooth muscle tone associated with partial bladder outlet obstruction is mediated via Rho-kinase.

Numerous studies have now demonstrated that lower urinary tract symptoms (LUTS) are associated with erectile dysfunction (ED) in men independent of age or general health. Because one-third of men over the age of 50 will develop LUTS and a recent study showed ED in 62% of patients presenting for LUTS, the importance of determining the mechanistic link between these two pathologies is clear. Using a rabbit model of partial bladder outlet obstruction (PBOO), a primary cause of LUTS, we have identified an increased basal corpus cavernosum smooth muscle (CCSM) tone associated with an elevated level of smooth muscle myosin (SMM) phosphorylation in PBOO compared with sham-operated control rabbits (sham). Results from in vitro kinase and phosphatase assays using purified smooth muscle myosin showed increased kinase and decreased phosphatase activities in cellular extracts from corpora cavernosa isolated from PBOO compared with sham rabbits. Increased Rho-kinase expression in the CCSM of PBOO rabbits was suggested by the observations that Rho-kinase inhibitors attenuated the increased kinase activity and were less effective in relaxing CCSM strips from PBOO vs. sham rabbits. This hypothesis was then confirmed by RT-PCR and Western blotting, which demonstrated increased expression of both isoforms of Rho-kinase (ROKalpha and ROKbeta). Increased SMM basal phosphorylation (necessary for SM contraction) in the CCSM of PBOO rabbits, mediated via an increase in Rho-kinase expression/activity, would be expected to make the CCSM more difficult to relax (necessary for erection), which suggests that the RhoA/Rho-kinase pathway as being involved in the mechanism for LUTS-associated ED.

Animals↗

Regional alterations in the expression of smooth muscle myosin isoforms in response to partial bladder outlet obstruction.

PURPOSE: Smooth muscle (SM) myosin (SMM) isoform composition is altered in response to partial bladder outlet obstruction (PBOO). A recent study showed that during PBOO the upper dome region of the bladder is subjected to greater expansion pressure than the base and regional differences in contractility exist in the detrusor of PBOO rabbits. We hypothesized that alteration in SMM isoform composition in response to PBOO may show regional heterogeneity. MATERIALS AND METHODS: Detrusor samples were obtained from 9 defined regions of the bladders from dysfunctional PBOO rabbits (greater than 30 voids per 24 hours) and sham operated adult New Zealand White rabbits. Reverse transcriptase-polymerase chain reaction, sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blotting were used to determine the relative levels of SMM isoform expression at the mRNA and protein levels. Contractile responses to bethanechol and KCl were also determined. RESULTS: Myosin isoform expression was uniform throughout the detrusor from sham operated subjects with all regions expressing SM-B almost completely. However, in response to PBOO the dome region showed approximately 70% SM-B and 30% SM-A isoforms, whereas the base region expressed only 35% SM-B and, thus, 65% SM-A. This change also correlated with an approximately 2-fold higher protein level expression of SM-B in the dome region of PBOO rabbit bladders. Expression of the SMemb SMM isoform was significantly increased in PBOO rabbits at the mRNA and protein levels but only in the dome region. Regional differences in SMM isoform expression in the PBOO rabbit bladders correlated with altered contractility. CONCLUSIONS: Alteration in SMM isoform composition in response to PBOO shows regional heterogeneity and may be involved in the mechanism responsible for regional localized differences in detrusor contractility in PBOO rabbits.

Animals↗

Prenatally detected primary megaureter: a role for extended followup.

PURPOSE: A high rate of spontaneous resolution of or decrease in urinary tract dilatation is expected for most cases of primary megaureter (PM). We analyzed our results with extended long-term nonsurgical treatment in a group of children diagnosed with prenatally detected PM. We also sought to determine the long-term safety of this approach and the clinical significance of residual hydroureteronephrosis (HUN) when complete resolution does not occur. MATERIALS AND METHODS: We reviewed our experience with 40 infants with prenatally detected hydronephrosis diagnosed as PM who were initially treated nonoperatively between 1986 and 1999. Patients were followed with ultrasonography, nuclear renography and, in some instances, excretory urogram until stable improvement or complete resolution of HUN was noted. Records for patients who specifically returned for long-term followup history and radiological imaging were also reviewed. RESULTS: Of 40 patients with 57 megaureters (17 with bilateral PMs) who were followed 4 infants (10%) with severe HUN were diagnosed with diminished renal function by nuclear renography and underwent surgical repair. A total of 27 infants (67.5%, 40 megaureters) with PM who were followed without surgical intervention returned for followup examination and imaging for a minimum of 24 months after initial diagnosis, for a mean of 6.8 years (range 24 to 210 months). Ultrasonography in these patients revealed complete resolution (Society for Fetal Urology grade 1 or less hydronephrosis) in 21 megaureters (52.5%) at a mean of 2.9 years and improved or stable HUN in 19 megaureters (47.5%). Antibiotic prophylaxis was administered to 12 patients beyond the first month of life and discontinued at a mean age of 19.9 months. A subgroup of 10 patients (16 megaureters) from this cohort returned for extended followup imaging at a mean of 13.4 years (range 84 to 210 months) following initial diagnosis. Four patients with documented resolution of HUN had no recurrence during long-term followup. One male with bilateral PMs diagnosed at birth that had been stable but were not resolved at 8-year followup suffered significant worsening in the degree of HUN, diminished renal function on 1 side and a renal stone on the contralateral renal unit at 14-year followup, despite remaining asymptomatic. CONCLUSIONS: Long-term followup of children with prenatally diagnosed PM with mild to moderate hydronephrosis confirms a high incidence of resolution and improvement. As we have documented 1 case of worsening HUN at 14-year followup, we believe that ultrasonography should be periodically continued until the child reaches adulthood, at least in instances where complete resolution of HUN is not documented.

Adolescent↗

Testicular microlithiasis and antisperm antibodies following testicular biopsy in boys with cryptorchidism.

PURPOSE: Testicular biopsy (TBx) performed during orchiopexy in boys with cryptorchidism can help to predict future semen analyses and possibly identify patients at risk for testicular cancer. It has been theorized that TBx can be detrimental to the long-term health of the testis. We examined testicular microlithiasis (TM) and antisperm antibody (ASA) production in cryptorchid TBx. MATERIALS AND METHODS: A total of 112 males underwent fertility evaluation. These patients had previously undergone orchiopexy and bilateral TBx (mean age 8.6 years) for unilateral or bilateral undescended testis. At a mean age of 19.6 years all patients underwent physical examination and scrotal ultrasound for evaluation of testis size, echotexture and abnormalities. Of 112 patients 57 also underwent direct Immunobead(R) assay with positive controls. Moving sperm free and/or bound to IgG bead complex were counted in the preparation. RESULTS: A total of 29 patients had bilateral and 83 had unilateral undescended testis. Of the 112 patients 26 were black and 86 were white. Four black patients (15.4%) and 4 white patients (4.7%) had testicular microlithiasis. Three patients had bilateral and 5 had unilateral diffuse TM. No tunica albuginea scars or testis masses were noted. In the 57 patients who underwent direct Immunobead assay no semen sample demonstrated evidence of forming bead-sperm complex, ie none had direct ASA. CONCLUSIONS: No patient exhibited evidence of direct ASA. Prepubertal open TBx does not increase the rate of TM. We found no evidence of additive testicular damage associated with TBx at the time of orchiopexy.

Adolescent↗

Overnight catheter drainage in children with poorly compliant bladders improves post-obstructive diuresis and urinary incontinence.

PURPOSE: Overnight catheter drainage (OCD) has been suggested as a treatment for boys with valve bladder syndrome as well as those with polyuric renal failure. We report our experience using overnight catheter drainage in children with poorly compliant bladders. MATERIALS AND METHODS: Between 1999 and 2004 OCD was initiated in 6 boys and 5 girls (median age 7.5 years) with poorly compliant bladders in whom aggressive daytime intermittent catheterization and anticholinergic use had failed. Etiologies of bladder dysfunction included posterior urethral valves in 1 case, The Hinman-Allen syndrome in 4, myelomeningocele in 2, neuroblastoma in 1, prune-belly syndrome in 1, transverse myelitis in 1 and sacral agenesis in 1. The amount of post-obstructive diuresis was calculated during urodynamics as the volume drained minus volume instilled divided by weight per hour. Other parameters evaluated included serum creatinine, degree of upper tract dilatation, and episodes of urinary tract infection (UTI) and incontinence. RESULTS: Median duration of OCD and followup was 28 months, respectively. One patient did not tolerate overnight drainage. Of 9 patients who were incontinent before OCD daytime urinary incontinence resolved in 6 and improved in 3. Recurrent febrile UTIs in 3 children were eliminated. Despite no change in serum creatinine with overnight drainage, 7 of 8 patients (88%) with upper tract dilatation improved on followup ultrasound. CONCLUSIONS: In select children with poorly compliant bladders OCD reduces diuresis, reduces the frequency of UTIs, improves upper tract dilatation and improves continence. Overnight drainage in conjunction with daytime clean intermittent catheterization may prove to be an alternative to bladder augmentation in select children with poorly compliant bladders and early stages of renal compromise.

Adolescent↗

Partial bladder outlet obstruction abolishes the receptor- and G protein-dependent increase in calcium sensitivity in rabbit bladder smooth muscle.

Partial bladder outlet obstruction (PBOO) alters the function of the whole bladder and produces specific alterations in the contractility of the bladder smooth muscle cell. The goal of this study was to test the hypothesis that PBOO affects smooth muscle contraction at the level of the receptor- and G protein-dependent increase in myofilament Ca2+ sensitivity. To address this question, we used alpha-toxin-permeabilized strips of bladder smooth muscle from control animals and animals subjected to 2 wk of PBOO. Increasing free [Ca2+] increased force in permeabilized strips from control animals; the addition of 10 microM carbachol and 10 microM GTP increased both the Ca2+ sensitivity of the contractions and the maximal levels of force attained. In contrast, although increases in [Ca2+] increased force in permeabilized strips from PBOO animals, the addition of carbachol and GTP had no additional effects. Myosin light chain phosphorylation levels increased with [Ca2+], and although they tended to be higher in strips from PBOO animals, they did not reach statistical significance. Assessment of G protein activity from both animal models suggests this is not a site responsible for the loss of carbachol and GTP enhancement of myofilament Ca2+ sensitivity. The addition of phorbol dibutyrate increased the Ca2+ sensitivity of force development in strips from both animal models, suggesting that an alteration in PKC signaling is not involved. Our results are consistent with the hypothesis that PBOO decreases receptor-mediated myofilament calcium sensitization and that the site of action is downstream from either the G proteins or PKC.

Animals↗

Murine in vitro whole bladder model: a method for assessing phenotypic responses to pharmacologic stimuli and hypoxia.

AIMS: Recent advances in genetic manipulation have allowed for over expression or deletion of selective genes in mice. This offers urologic investigators new means of understanding bladder function in the context of normal development or the response to outlet obstruction. It is important to correlate any genetic manipulations in mice with specific phenotypic properties such as voiding patterns, or muscle strip physiology. We describe a simple in vivo whole bladder preparation that may be used to study the phenotypic changes in bladder function. METHODS: Murine bladders were mounted on a 30 gauge needle and mounted in an organ chamber containing a physiologic buffer solution. Passive bladder properties were assessed with cystometry, and active contractile responses were measured in response to electrical field stimulation and agonists. The effects of hypoxia were also studied. RESULTS: Compliance in the murine bladder is dependent upon actin myosin interactions, and increased in the presence of calcium free buffer and EGTA. The sarcoplasmic reticulum plays a smaller role in the contraction of murine bladder than in other species. Murine bladder smooth muscle demonstrated a remarkable ability to withstand hypoxia. CONCLUSIONS: This simple model can be adapted to help study the murine bladder smooth muscle phenotype under highly controlled circumstances.

Adenosine Triphosphate↗

Renal and adrenal tumors in children.

Survival rates for children with kidney tumors approach 90% for even the most advanced stages of disease, but the surgical management of large lesions remains challenging. With the development of additional chemotherapeutic regimens and the use of radiation therapy, survival rates have improved dramatically. The National Wilms' Tumor Study has conducted four long-term studies addressing how adjunctive therapy may be tailored optimally to maximize survival and minimize the exposure to chemotherapy and radiation therapy.

Adrenal Gland Neoplasms↗

Smooth muscle hypertrophy following partial bladder outlet obstruction is associated with overexpression of non-muscle caldesmon.

Partial bladder outlet obstruction (PBOO) induces remodeling of urinary bladder smooth muscle (detrusor). We demonstrate an increase in bladder wall mass, muscle bundle size, and a threefold increase in the cross-sectional area of detrusor myocytes following PBOO in male New Zealand White rabbits compared to that of controls. Some bladders with detrusor hypertrophy function close to normal (compensated), whereas others were dysfunctional (decompensated), showing high intravesical pressure, large residual urine volume, and voiding difficulty. We analyzed the expression of smooth muscle-specific caldesmon (h-CaD) and non-muscle (l-CaD) by Western blotting, RT-PCR, and real-time PCR. The expression of l-CaD is increased significantly at the mRNA and protein levels in the decompensated bladders compared to that of normal and compensated bladders. The CaD was also co-localized with myosin containing cytoplasmic fibrils in cells dissociated from obstructed bladders and cultured overnight. Our data show that the inability of decompensated bladders to empty, despite detrusor hypertrophy, is associated with an overexpression of l-CaD. The level of l-CaD overexpression might be a useful marker to estimate the degree of detrusor remodeling and contractile dysfunction in PBOO.

Animals↗

Decrease in maximal force generation in the neonatal mouse bladder corresponds to shift in myosin heavy chain isoform composition.

PURPOSE: A change in calcium handling has been proposed as the cause of decreased maximal force generation by neonatal bladders with growth. Recent studies suggest that increased myosin heavy chain isoform SM1 increases force generation. We studied force generation in neonatal mouse bladders to determine if decreases in SM1 corresponded with decreased force. MATERIALS AND METHODS: C57Bl/6 mice were studied from birth to 12 weeks of life (adulthood). The bladder strip contractile response to KCl and bethanechol was followed by the inhibition of rho-kinase activity by Y-27632. The mRNA levels for SM1/SM2 were determined using reverse transcriptase-polymerase chain reaction and protein levels were determined using sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Muscle fraction per cross-sectional area was determined by trichrome staining. RESULTS: Newborn bladders generated significantly more tension in response to KCl (43.3 vs 17.4 mN/mm2, p = 0.02) and bethanechol (40.6 vs 11.9 mN/mm2, p = 0.05) than adult bladders. Inhibition of rho-kinase resulted in similar decreases in tension in all bladders. SM1 mRNA decreased slightly from 60% at birth to 50% at 12 weeks. SM1 protein decreased from 72.5% at birth to 50% by 3 weeks and it remained stable at 12 weeks. Total myosin per gm protein remained stable. Muscle fraction decreased from 63.8% at birth to 58.6% at 12 weeks (p = 0.4). CONCLUSIONS: We noted a decrease in SM1 that corresponded to a decrease in bladder force generation. The concept that SM1 contributes to the optimal assembly of myosin filaments suggests that changes in myosin isoforms may have a role in the decrease in voiding pressures seen in normal children.

Animals↗

Experience with testis sparing surgery for testicular teratoma.

PURPOSE: Testicular teratoma is a rare neoplasm affecting the pediatric population and has classically been reported to be the second most common testis tumor in children behind yolk sac tumors. Testicular teratomas are benign and partial orchiectomy may be considered. We describe our single institution experience with testicular teratoma and definitive treatment with testis preserving surgery. MATERIALS AND METHODS: We reviewed the pathology records at our institution for all testicular and paratesticular tumors diagnosed between 1976 and November 2002 in males younger than 18 years. We specifically examined the prepubertal incidence of teratoma, including epidermoid cysts, and our experience with testis preserving surgery. Preoperative and postoperative ultrasonography images were used to calculate the atrophy index following surgery. Patients were contacted for long-term followup. RESULTS: Of 77 primary testicular and paratesticular tumors 38 were diagnosed in prepubertal boys (age younger than 13 years) including 11 mature teratomas and 5 epidermoid cysts. Mean patient age at treatment was 34.4 months (range 4 months to 10 years). All boys presented with a painless scrotal mass, cystic foci within an intratesticular mass on ultrasound and a normal alpha-fetoprotein level. Of the 16 boys with benign teratomas 13 (81%) were treated with a testis sparing procedure. At a mean 7-year followup no patient has presented with recurrent tumor in the ipsilateral or contralateral testicle. Postoperative physical examination and scrotal ultrasound were obtained in 9 patients at a median followup of 10.2 months, and there was no evidence of testicular atrophy or persistent discomfort. CONCLUSIONS: Unlike previously published series based on tumor registries, benign teratoma was the most common pediatric testicular tumor treated at our institution. Our single institution experience with testis preservation and long-term followup confirms the role and safety of this technique. Testis sparing surgery remains our technique of choice for testicular teratoma.

Child↗

Over expression of smooth muscle specific caldesmon by transfection and intermittent agonist induced contraction alters cellular morphology and restores differentiated smooth muscle phenotype.

PURPOSE: The thin filament associated protein h-caldesmon (h-CaD) modulates actin myosin interaction and contraction. Bladder outlet obstruction and detrusor hypertrophy are associated with the over expression of the nonmuscle CaD isoform l-CaD. It implies a poorly differentiated state of bladder myocytes and cytoskeletal remodeling in detrusor hypertrophy. We determined if h-CaD expression can be increased in a unique bladder smooth muscle (BSM) cell line derived from obstructed rabbit bladder smooth muscle that over expresses l-CaD. We examined whether the genetic restoration of h-caldesmon is possible in bladder smooth muscle cells by transfection or by agonist mediated contraction and whether this manipulation would alter cellular morphology. MATERIALS AND METHODS: BSM cells were transfected with chicken h-CaD cDNA inserted into a mammalian vector. In another experiment BSM cells underwent intermittent bethanechol induced stimulation. h-CaD mRNA and protein were quantified with reverse transcriptase-polymerase chain reaction and Western blot analyses. Cell morphology was assessed using phase, video and confocal microscopy after double immunostaining with antibodies against alpha-actin and caldesmon. RESULTS: Reverse transcriptase-polymerase chain reaction using primers specific for the transfected vector and h-CaD cDNA confirmed stable transfection of cells and increased content of h-CaD mRNA. Following bethanechol induced intermittent contraction Western blotting revealed 80% relative over expression of h-CaD in treated transfected cell lines (p <0.05) and 74% (not significant) in treated nontransfected controls. Confocal immunofluorescence microscopy revealed CaD in the cytoplasmic filaments co-localized to alpha-actin in the main cell body and perinuclear region in transfected cells, in contrast to the diffuse, irregular distribution of these filaments in control cells. CONCLUSIONS: A unique bladder myocyte cell line was successfully and stably transfected with h-CaD cDNA. We show that agonist induced intermittent contraction preferentially increases h-CaD expression, the predominant CaD in nonobstructed bladder smooth muscle, and the restoration of h-CaD alters cell morphology and the organization of cytoplasmic filaments in cells derived from obstructed rabbit detrusor musculature.

Bethanechol↗