Human Bladder Neck Research Articles

Phosphodiesterase type 4 inhibition enhances nitric oxide- and hydrogen sulfide-mediated bladder neck inhibitory neurotransmission

Nitric oxide (NO) and hydrogen sulfide (H2S) play a pivotal role in nerve-mediated relaxation of the bladder outflow region. In the bladder neck, a marked phosphodiesterase type 4 (PDE4) expression has also been described and PDE4 inhibitors, as rolipram, produce smooth muscle relaxation. This study investigates the role of PDE4 isoenzyme in bladder neck gaseous inhibitory neurotransmission. We used Western blot and double immunohistochemical staining for the detection of NPP4 (PDE4) and PDE4A and organ baths for isometric force recording to roflumilast and tadalafil, PDE4 and PDE5, respectively, inhibitors in pig and human samples. Endogenous H2S production measurement and electrical field stimulation (EFS) were also performed. A rich PDE4 and PDE4A expression was observed mainly limited to nerve fibers of the smooth muscle layer of both species. Moreover, roflumilast produced a much more potent smooth muscle relaxation than that induced by tadalafil. In porcine samples, H2S generation was diminished by H2S and NO synthase inhibition and augmented by roflumilast. Relaxations elicited by EFS were potentiated by roflumilast. These results suggest that PDE4, mainly PDE4A, is mostly located within nerve fibers of the pig and human bladder neck, where roflumilast produces a powerful smooth muscle relaxation. In pig, the fact that roflumilast increases endogenous H2S production and EFS-induced relaxations suggests a modulation of PDE4 on NO- and H2S-mediated inhibitory neurotransmission.

Powerful relaxation of phosphodiesterase type 4 inhibitor rolipram in the pig and human bladder neck.

Phosphodiesterase type 5 (PDE5) inhibitors act as effective drugs for the treatment of lower urinary tract symptom (LUTS). There is a poor information, however, about the role of the PDE4 inhibitors on the bladder outflow region contractility. To investigate PDE4 expression and the relaxation induced by the PDE4 inhibitor rolipram versus that induced by the PDE5 blockers sildenafil and vardenafil, in the pig and human bladder neck. Immunohistochemistry for PDE4 expression, myographs for isometric force recordings and fura-2 fluorescence for simultaneous measurements of intracellular Ca2+ concentration ([Ca2+]i ) and tension for rolipram in bladder neck samples were used. PDE4 expression and relaxations to PDE4 and PDE5 inhibitors and simultaneous measurements of [Ca2+]i and tension. PDE4 expression was observed widely distributed in the smooth muscle layer of the pig and human bladder neck. On urothelium-denuded phenylephrine (PhE)-precontracted strips of pig and human, rolipram, sildenafil and vardenafil produced concentration-dependent relaxations with the following order of potency: rolipram> > sildenafil>vardenafil. In pig, the adenylyl cyclase activator forskolin potentiated rolipram-elicited relaxation, whereas protein kinase A (PKA) blockade reduced such effect. On potassium-enriched physiological saline solution (KPSS)-precontracted strips, rolipram evoked a lower relaxation than that obtained on PhE-stimulated preparations. Inhibition of large (BKCa ) and intermediate (IKCa ) conductance Ca2+ -activated K+ channels, neuronal voltage-gated Ca2+ channels, nitric oxide (NO) and hydrogen sulfide (H2 S) synthases reduced rolipram responses. Rolipram inhibited the contractions induced by PhE without reducing the PhE-evoked [Ca2+]i increase. PDE4 is present in the pig and human bladder neck smooth muscle, where rolipram exerts a much more potent relaxation than that elicited by PDE5 inhibitors. In pig, rolipram-induced response is produced through the PKA pathway involving BKCa and IKCa channel activation and [Ca2+]i desensitization-dependent mechanisms, this relaxation also being due to neuronal NO and H2S release.

Tadalafil Enhances the Inhibitory Effects of Tamsulosin on Neurogenic Contractions of Human Prostate and Bladder Neck

Lower urinary tract symptoms secondary to benign prostatic hyperplasia (BPH-LUTSs) may be associated with erectile dysfunction (ED). Phosphodiesterase type 5 (PDE5) inhibitors used for treating ED have shown clinical benefit in patients with LUTS but their actions in human LUT tissues are not well defined. To determine the effects of the long-acting PDE5 inhibitor, tadalafil, on smooth muscle tone in human prostate and bladder neck as well as to evaluate the influence of tadalafil on the efficacy of the α-adrenergic receptor antagonist, tamsulosin, in inhibiting contractile responses in these tissues. Strips of human peripheral prostate (HPP), human internal prostate (HIP), and human bladder neck (HBN) were obtained from organ donors and patients with BPH. The strips were then disposed in organ baths to evaluate nitric oxide/cyclic guanosine monophosphate (cGMP)-mediated relaxation and cGMP kinetics in HPP and HIP, and electrical field stimulation (EFS)-induced neurogenic contractions in HPP and HBN. Tadalafil-induced effects on sodium nitroprusside (SNP)-induced relaxation and cGMP accumulation in HPP and HIP and influence of tadalafil and tamsulosin on EFS-induced contractions of HPP and HBN. SNP-induced relaxation of HPP and HIP was significantly potentiated by tadalafil (30-60 nM). SNP-induced cGMP accumulation in HPP and HIP was enhanced by tadalafil (30-60 nM), but significant difference was only obtained in HPP. EFS-induced contractions sensitive to tetrodotoxin in HPP were significantly inhibited by tadalafil (30 nM) but not by tamsulosin (0.01-100 nM) or vehicle. Further inhibition of neurogenic responses in HPP was achieved by combining tadalafil and tamsulosin treatments. Tamsulosin, but not tadalafil, significantly reduced EFS-induced contractions in HBN, but the coadministration of both therapies resulted in additional inhibition of contractions. While tadalafil enhances cGMP accumulation and potentiates prostate relaxation, tadalafil combined with tamsulosin results in enhanced inhibition of neurogenic contractions of HPP and HBN.

Functional evidence of nitrergic neurotransmission in the human urinary bladder neck

Nitric oxide (NO) is involved in the non-adrenergic non-cholinergic (NANC) inhibitory neurotransmission of the lower urinary tract. However, functional evidence of this involvement in the human urinary bladder neck has not been consistently demonstrated. Therefore, the current study investigates the relaxations to endogenously released and/or exogenously added NO, in the human bladder neck. Urothelium-denuded bladder neck strips were dissected and mounted in isolated organ baths, containing a physiological saline solution (PSS) at 37 °C and continuously gassed with 5% CO 2 and 95% O 2, for isometric force recording. The relaxations to transmural nerve stimulation (EFS) or to exogenously applied NO, as an acidified solution of NaNO 2 were carried out on strips precontracted with phenylephrine, and treated with guanethidine and atropine, to block noradrenergic neurotransmission and muscarinic receptors, respectively. EFS (0.5–16 Hz) and exogenous NaNO 2 (1 μM to 1 mM) evoked frequency- and concentration-dependent relaxations, respectively. The nerve responses were abolished by the blockade of neuronal voltage-activated Na + channels with tetrodotoxin, indicating their neurogenic character. N G-nitro- l-arginine ( l-NOARG), a NO synthase inhibitor, abolished the relaxations to nerve stimulation, which were partially reversed by the substrate of NO synthesis l-arginine. l-NOARG failed to modify the relaxations to exogenous NaNO 2. These results suggest that NO is the major NANC inhibitory neurotransmitter in the human urinary bladder neck. Blockers of NO synthase could be useful in therapy for the urinary incontinence produced by intrinsic sphincteric deficiency.

Human prostatic urethra expresses vitamin D receptor and responds to vitamin D receptor ligation

Chronic inflammation is now considered a determinant of benign prostatic hyperplasia (BPH), promoting, together with the hormonal milieu, prostate overgrowth and lower urinary tract symptoms (LUTS). Prostatic urethra actively participates in determining progression of LUTS associated with BPH. To investigate the expression of the vitamin D receptor (VDR) and the ability of the VDR agonist elocalcitol to reduce inflammatory responses in human prostatic urethra (hPU) cells. Human prostatic urethra, prostate and bladder neck were obtained from patients affected by BPH. Immunohistochemical studies for VDR expression were performed in tissue samples, from which primary cell cultures were also derived. In hPU cells, proliferation and chemiotaxis were studied, along with Rho kinase (ROCK) activity (MYPT-1 phosphorylation) by western blot. Quantitative RT-PCR was performed for VDR, cyclooxygenase (COX-2), and interleukin (IL)-8 expression. Urethra displays higher VDR expression compared to prostate and bladder neck tissues. The VDR agonist elocalcitol partially reverts COX-2 and IL-8 mRNA upregulation induced by a pro-inflammatory cytokine mixture (IL-17, interferon-γ, tumor necrosis factor-α) and inhibits cell migration in urethral cells. Elocalcitol prevents activation of ROCK, as previously demonstrated in bladder and prostate cell cultures. Our results suggest that prostatic urethra is, within the lower urinary tract, a novel target for VDR agonists, as shown by the capacity of elocalcitol to inhibit ROCK activity and to limit inflammatory responses in human primary urethra cells.

Comparisons of the responses of anterior and posterior human adult male bladder neck smooth muscle to in vitro stimulation

To evaluate differing methods of stimulation on strips of human bladder neck smooth muscle and compare muscle taken from the anterior and posterior aspects. Samples of adult human male bladder neck muscle were obtained from patients undergoing open radical prostatectomy. Muscle was taken from either the anterior or posterior (nine and six patients, respectively) aspects of the bladder neck. Muscle strips dissected from these samples were suspended in the Brading-Sibley organ bath. The strips were superfused with 100 mm KCl-enriched Krebs' solution for 4 min to determine viability. This allowed experimentation on 17 strips from the anterior aspect of the bladder neck and 13 from the posterior bladder neck. These remaining strips were then superfused either with various concentrations (x10(-7) to x10(-3)m) of carbachol or noradrenaline in Krebs' solution, for 15 s. A further set of strips (eight from anterior, six from posterior) was suspended and responses to electrical field stimulation (EFS) with varying parameters were measured. Each EFS experiment was repeated after a 15 min exposure to 10(-3)m atropine, and again after a 15 min exposure 10(-7)m tetrodotoxin (TTX). Tension responses produced in these series of experiments were measured using strain gauges and analysed using data acquisition software. Student's t-test was used for the statistical analysis. All muscle strips included in the study responded to EFS. The magnitude of this contraction is frequency dependent. The contractions were abolished by superfusion of the muscle strips with atropine. There was no further suppression of the contractile response on addition of TTX. Posterior bladder neck samples had a greater mean contractile response per unit mass than anterior strips at all frequencies of >1 Hz, and significantly more at 20 and 30 Hz. There was a concentration-dependent response in bladder neck contraction to carbachol but only in the strips from the anterior bladder neck at concentrations of <10(-3)m. Posterior bladder neck strips did not significantly contract upon application of carbachol. Similarly, there was a concentration-dependent response to noradrenaline. Responses to noradrenaline were not uniform around the bladder neck, but not significantly different. Carbachol was the more 'potent' stimulator in anterior smooth muscle strips, but again the differences between agonists were not statistically significant. These experiments show physiological variability around the circumference of the human male bladder neck. The posterior bladder neck shows significantly stronger contraction to alpha-adrenergic agonists compared with cholinergic agonists; the anterior bladder neck does not have a similarly significant differential response. The uniform response to noradrenaline may underlie the bladder neck's role in the prevention of retrograde ejaculation. The differential responses to carbachol may reflect differences in the embryological derivation of the anterior and posterior bladder neck fibres or in their innervation. Some of these differences may have clinical importance through the action of therapeutic agents.

Human Bladder as a Novel Target for Vitamin D Receptor Ligands

Human prostate is now considered a target for vitamin D receptor (VDR) ligands, such as BXL-628. Because BXL-628 inhibited prostate growth without interfering with androgen signaling, it represents a new option for benign prostate hyperplasia (BPH) therapy. However, BPH symptoms are related not only to prostate size, but also to compensatory bladder hypertrophy and eventual overactivity. We now report that human bladder expresses VDR (determined by real-time PCR immunohistochemistry and Western blot) and responds to VDR agonists, such as the natural ligand, calcitriol, and its synthetic and less hypercalcemic derivative, BXL-628. Experiments were conducted with stromal cells derived from human bladder neck obtained at surgery from BPH patients. BXL-628 counteracted keratinocyte growth factor (KGF) and androgen-induced cell proliferation and stimulated apoptosis with a parallel reduced expression of the survival oncoprotein Bcl-2. Prolonged serum starvation time-dependently pushed bladder stromal cells to express activated myofibroblast markers, such as desmin and smoothelin, without changing other contractile-related proteins and intermediate filaments, such as vimentin. Chronic exposure to BXL-628 prevented starvation-induced cell phenotype modification. Because hypertrophy and starvation-induced bladder remodeling are supposed to underlie bladder overactivity, it is possible that BXL-628 might be helpful in reducing not only cumbersome symptoms related to prostate overgrowth, but also those related to bladder irritation.

Muscle Systems Of The Lower Urinary Tract Of The Male Rhesus Monkey (Macaca Mulatta): Histomorphology And 3-dimensional Reconstruction

The structure and function of the lower urinary tract are still a subject of controversial discussion. Experiments in various animals, including rhesus monkeys, are often performed to improve the understanding of human physiology without adequate knowledge of anatomical differences. Therefore, a detailed study of the lower urinary tract of the male rhesus monkey (Macaca mulatta) was performed to elucidate anatomical correspondences in rhesus monkeys and humans. Lower urinary tract anatomy and histomorphology were investigated in male rhesus monkeys on serial sections. To differentiate striated and smooth muscle immunohistochemical staining was done. Three-dimensional reconstructions were developed to demonstrate the topography of the muscle systems. We identified certain systems, including detrusor musculature extending on the bladder neck, a ventral longitudinal muscle system of the bladder neck, continuation of the musculature of the ureters to the verumontanum, a urethral sphincter consisting of a striated and a smooth muscle part, musculature between the urethra and rectum, and a striated longitudinal muscle system ventral to the urethral sphincter. The prostate gland of the rhesus monkey does not encircle the urethra but is attached dorsolateral. The internal sphincter (musculus sphincter vesicae) of humans does not exist in the rhesus monkey. The longitudinal systems of the urethra differ significantly from those in humans. Due to significant differences in lower urinary tract anatomy the suitability of the male rhesus monkey seems limited as an animal model for humans. It is not suitable for studying the longitudinal muscle systems of the human bladder neck.

INEFFICIENT URETHRAL MILKING SECONDARY TO URETHRAL DYSFUNCTION AS AN ADDITIONAL RISK FACTOR FOR INCONTINENCE AFTER RADICAL PROSTATECTOMY

Continence after radical prostatectomy is thought to depend completely on the striated urethral sphincter. However, some patients complain only of occasional post-void dribbling. Therefore, we determined whether urethral dysfunction may be another cause of incontinence. The sensory threshold of electric stimulation was measured by double ring electrodes in the membranous urethra and 2.5 cm. distal in 29 men before and in 29 after radical retropubic prostatectomy. In addition, voiding cystourethrography was performed in 66 patients before and in 49 after surgery to determine complete post-void urethral emptying or milking. The mean sensory threshold of the membranous urethra was 15 +/- 3 mA. preoperatively versus 38 +/- 17 postoperatively (p <0.0001). The sensory threshold 2.5 cm. further distal was 12 +/- 5 mA. before and 10 +/- 4 after radical prostatectomy, which was not statistically significant. Postoperatively in completely continent patients and in those with dribbling the mean threshold was 32 +/- 12 and 43 +/- 18 mA. in the membranous urethra (p = 0.09), and 11 +/- 4 and 9 +/- 4 mA. in the bulbar urethra, respectively, which was not statistically significant. Of the 66 patients 36 (55%) showed post-void urethral milking before surgery but only 8 of 49 (16%) showed it postoperatively (chi-square test p <0.0001), including 7 who were completely continent and 1 who complained of occasional post-void dribbling. After radical prostatectomy sensitivity of the membranous but not of the bulbar urethra is affected, correlating with postoperative continence. In addition, post-void dribbling seems to be associated with the loss of urethral milking. We conclude that preserving urethral function is another important continence factor after radical prostatectomy.

MORPHOLOGICAL ASPECTS OF THE FEMALE PIG BLADDER NECK AND URETHRA: QUANTITATIVE ANALYSIS USING COMPUTER ASSISTED 3-DIMENSIONAL RECONSTRUCTIONS

To investigate whether the pig is a suitable model for studies of lower urinary tract function and dysfunction, we sought to determine the morphology of the female pig bladder neck and urethra. Computer assisted 3-dimensional (D) reconstructions from step serial histological sections were used for visualization of the spatial relationships between neighboring urethral wall components, and the quantification of these components in the bladder neck and along the urethra. Step serial histological paraffin sections from the bladder neck and urethra of 6 female pigs, stained with Masson's trichrome, were used to generate computer assisted 3-D reconstructions using MacStereology (Ranfurly MicroSystems Ltd., Airdrie, United Kingdom) as the 3-D software package. The bladder neck and urethral anatomy revealed well defined smooth and striated muscle layers that varied in location, regional distribution and orientation. Circular smooth muscle was maximally developed in the mid urethra, at which point maximal urethral pressure was observed. The longitudinal smooth muscle layer appeared continuous with the detrusor, implicating a possible role in urethral shortening at the onset of voiding. A small circular and longitudinal striated muscle component was present in the distal urethra. Anatomical differences exist between the female pig and human bladder neck and urethra, which were successfully highlighted using computer assisted 3-D reconstructions from step serial histological paraffin sections.

In vitro studies on L-771,688 (SNAP 6383), a new potent and selective α 1A-adrenoceptor antagonist

L-771,688 (SNAP 6383, methyl(4 S)-4-(3,4-difluorophenyl)-6-[(methyloxy)methyl]-2-oxo-3-[({3-[4-(2-pyridinyl)-1-piperidinyl]propyl}amino)carbonyl]-1,2,3,4-tetrahydro-5-pyrimidinecarboxylate) had high affinity ( K i ≤1 nM) for [ 3H]prazosin binding to cloned human, rat and dog α 1A-adrenoceptors and high selectivity (>500-fold) over α 1B and α 1D-adrenoceptors. [ 3H]Prazosin/(±)-β-[ 125I]-4-hydroxy-phenyl)-ethyl-aminomethyl-teralone([ 125I]HEAT) binding studies in human and animal tissues known to contain α 1A and non-α 1A-adrenoceptors further demonstrated the potency and α 1A-subtype selectivity of L-771,688. [ 3H]L-771,688 binding studies at the cloned human α 1A-adrenoceptors and in rat tissues indicated that specific [ 3H]L-771,688 binding was saturable and of high affinity( K d=43–90 pM) and represented binding to the pharmacologically relevant α 1A-adrenoceptors. L-771,688 antagonized norepinephrine-induced inositol-phosphate responses in cloned human α 1A-adrenoceptors, as well as phenylephrine or A-61603 ( N-[5-4,5-dihydro-1 H-imidazol-2yl)-2-hydroxy-5,6,7,8-terahydro-naphthlen-1-yl] methanesulfonamide hydrobromide) induced contraction in isolated rat, dog and human prostate, human and monkey bladder neck and rat caudal artery with apparent K b values of 0.02–0.28 nM. In contrast, the contraction of rat aorta induced by norepinephrine was resistant to L-771,688. These data indicate that L-771,688 is a highly selective α 1A-adrenoceptor antagonist.

A double-label immunohistochemical study of intramural ganglia from the human male urinary bladder neck.

Double-label immunocytochemistry was used to investigate the colocalisation of various neuropeptides and the enzymes nitric oxide synthase (NOS) and tyrosine hydroxylase (TH) in intramural ganglia of the human male urinary bladder neck and trigone. Postmortem specimens were obtained from 7 male infants and children ranging in age from 2 mo to 3 y who had died as a result of cot death or accidental trauma. On average 60% of the intramural neurons were non-TH-immunoreactive (-IR) (i.e. presumptive cholinergic) and 40% were TH- and D beta H-IR (i.e. noradrenergic). Within the non-TH-IR population, calcitonin gene-related peptide (CGRP) was found in 65% of cells, neuropeptide Y (NPY) in 90%, nitric oxide synthase (NOS) in 45%, somatostatin (SOM) in 90%, and vasoactive intestinal polypeptide (VIP) in 40%. The corresponding values for the TH-IR neurons were CGRP (54%), NPY (70%), NOS (58%), SOM (73%) and VIP (40%). All the observed bombesin (BOM)-immunoreactivity was colocalised with TH while 90% of VIP and almost all the CGRP was colocalised with NPY. Less than 5% of neurons were immunoreactive for substance P (SP) or met-enkephalin (m-ENK) and some of these also contained TH. Varicose nerve fibres were seen in close proximity to some of the intramural neurons, the majority of such varicosities showing immunoreactivity to CGRP, VIP or TH. Less common were pericellular varicosities immunoreactive to NPY, SOM or SP. These results demonstrate the neurochemical heterogeneity of intramural neurons in the human bladder neck and provide indirect evidence for the complexity of the peripheral innervation of the human urinary bladder.

Localization of nitric oxide synthaseactivity in the human lower urinary tract and its correlation with neuroeffector responses

The present study was designed to correlate the localization of nitric oxide synthase (NOS) activity to nerve-induced smooth muscle responses in the human lower urinary tract. Nerve-induced smooth muscle activity was studied in the human lower urogenital tract. NOS activity was studied by measurement of citrulline formation and guanylate cyclase activity. Nerve-induced contractions in the human detrusor muscle, bladder neck, and prostatic urethra were not significantly enhanced by the NOS inhibitor N omega-nitro-L-arginine methyl ester (L-NAME). In the prostatic urethra, relaxations to transmural nerve stimulation were obtained after increase in tension. The relaxations were abolished by L-NAME and restored by L-arginine. Nerve-induced relaxations were occasionally obtained in the bladder neck, whereas nerve-induced relaxations were never obtained in the detrusor muscle. Citrulline formation was highest in the prostatic urethra, it was intermediate in the bladder neck, and it was less pronounced in the detrusor muscle. Guanylate cyclase activity was also highest in the prostatic urethra, whereas there was no significant difference in guanylate cyclase activity in the bladder neck and detrusor muscle. The nerve-induced smooth muscle responses and the localization of NOS activity were in good agreement. Thus, in areas where marked relaxations to nerve stimulation were obtained, there was also a high NOS activity. The data suggest that nitric oxide is a mediator for the neurogenic dilation of the bladder neck and urethra during the micturition reflex.

HUMAN LUNG, BLADDER AND HEAD AND NECK TUMORS AS COMPARED TO THEIR ADJACENT NORMAL-TISSUES HAVE ELEVATED AP-1 ACTIVITY AND RECOGNIZE SEQUENCE ELEMENTS OF HIV-1 LTR

We have previously reported the specific binding of nuclear factor AP-1 isolated from human breast MDA MB 468 and HeLa cervical tumor cell lines to oligonucleotides complementary to three newly elucidated sequences within the HIV-1 LTR. These synthesized oligonucleotides, which bear high homology to the AP-1 recognition sequence, were used in the present study in gel retardation assays together with unfractionated nuclear protein extracts from human lung, bladder and head and neck tumors and adjacent normal tissue to study the role of the AP-1 protein in the regulation of HIV-1 expression. We found increased binding of AP-1 to these oligonucleotides in 9/12 lung tumors, 9/14 bladder tumors and 7/7 head and neck tumors as compared to adjacent normal tissues. This confirms previous results obtained when using MDA MB 468 and HeLa nuclear protein extracts. These results indicate that, AP-1 could be contributing to the HIV-1 transcriptional regulation through its interaction with the AP-I binding sites of HIV-I LTR.

P-244 - Distribution of Neuropeptide Y (NPY) and its binding sites in human bladder neck: morphological and quantitative analysis.

P-244 - Distribution of Neuropeptide Y (NPY) and its binding sites in human bladder neck: morphological and quantitative analysis.

Distribution of neuropeptide Y (NPY) and its binding sites in human lower urinary tract. Histological analysis

Neuropeptide Y (NPY), consisting of 36 amino acids, has been reported to coexist usually with noradrenaline in peripheral sympathetic neurons. For the purpose of clarifying the physiological role of NPY in lower urinary tract, I studied the existence of NPY and its binding sites around human bladder neck. The distribution of NPY in bladder neck was identified by means of immunohistochemistry. Abundant NPY fibers run parallel to muscle fibers, and NPY positive neuron plexus was recognized just beneath the serosa. Binding assay and autoradiographic study indicated the abundant NPY specificities in the epithelial and muscle layers from bladder neck to prostatic urethra. Present study revealed that NPY might be a possible neuromodulator in lower urinary tract, cooperating with noradrenaline.

Antispasmodic effects of flavoxate, MFCA,and REC 15/2053 on smooth muscle of human prostate and urinary bladder

The antispasmodic effects of the flavone compounds flavoxate hydrochloride, 3-methylflavone carboxylic acid (MFCA), and REC 15/2053 (and in the case of the detrusor, oxybutynin), on the human detrusor, prostatic adenoma, prostatic capsule, and bladder neck, were studied by the in vitro isometric method. All the compounds inhibited, in different orders of potency, potassium-induced contractions of the tissues. Flavoxate showed a slightly greater activity than the other two compounds in the prostatic and bladder neck tissues. However, REC 15/2053 displayed greater activity in the detrusor than in the other tissues. The relaxant effect on the prostatic tissues suggests a potential use for these compounds in benign prostatic obstruction.

Vasoactive Intestinal Polypeptide Concentration in Human Bladder Neck Smooth Muscle and its Influence on Urodynamic Parameters

Three human studies were performed to evaluate the influence of vasoactive intestinal polypeptide (VIP) on bladder and urethral function. Bladder neck smooth muscle biopsies were obtained from nine men with functional bladder neck obstruction, from 10 men with medium sized benign prostatic hypertrophy and from four patients with a normal infravesical outlet. The biopsies were analysed for VIP by radioimmunoassay and by immunohistochemistry. No differences were found between the groups. Pressure-flow-EMG studies were performed in five men and urethrocystometry was performed in six women at rest, repeated coughing and at squeezing before, during and after VIP 3 micrograms/kg X h intravenously. No systematic changes developed in any of the urodynamic parameters.

The Structure of the Female Lower Urinary Tract and Pelvic Floor

This article presents the salient features of the histology of the human female bladder, bladder neck, and urethra. Also described are the structure and relationships of the pelvic floor, with particular emphasis on aspects that concern the functional control of the urethra.

The autonomic innervation of the human urinary bladder, bladder neck and urethra: a histochemical study.

The autonomic innervation of smooth muscle in fresh biopsy specimens of the human urinary bladder, bladder neck and urethra has been examined using specific neurohistochemical techniques. Acetylcholinesterase-containing nerve fibers have been demonstrated amongst the smooth muscle cells in all the biopsy samples. Enzyme-positive fibers formed a plexus, the density of which varied dependent upon the region from which the biopsy material was obtained. Catecholamine (noradrenaline)-containing autonomic nerve fibers were observed amongst smooth muscle cells of the vesico-urethra junction; other than for perivascular nerve plexuses. Noradrenergic fibers were absent from biopsy samples of other regions. Juxtamural, acetylcholinesterase-positive neurones were present in some samples, and a proportion of these cell bodies were closely related to noradrenergic nerve terminal regions. These findings are discussed in relation to those of other workers who have examined the innervation of the mammalian lower urinary tract.