Decrease In Urethral Pressure Research Articles

Noninvasive estimation of the pressure profile in the male urethra using ultrasound imaging.

Decreased prostatic compliance as a result of benign prostatic enlargement can result in bladder outlet obstruction. This changes the urethral pressure profile during voiding. In this study, the authors propose noninvasive estimation of this pressure profile. In four soft tissue mimicking models of the urethra with increasing degree of obstruction, the authors measured deformation of the wall during flow, using ultrasound imaging. Combined with estimates of the model compliance, the authors were able to estimate the pressure profile. First, the compliances (Young's moduli) of the four models were derived by applying static luminal pressure and measuring the resulting strain of the tissue using an ultrasound imaging system. Next, continuous flow was applied to the models and the strain in the urethral wall was measured similarly. The luminal pressure profile was estimated from the strain (measured under continuous flow conditions) and the derived compliance (measured under static pressure conditions). The estimated pressures up- and downstream of the obstruction were compared with the corresponding measured pressures. In the obstructed region, the strain gradient was estimated using linear regression. The luminal pressure values estimated from the ultrasound data up- and downstream of the obstruction were not significantly different from the corresponding measured pressures. The general pressure profile showed a decrease along the length of the obstruction followed by a small increase after the obstruction. The strain gradient in the obstructed region reflected the decrease in urethral pressure and increased with flow rate and degree of obstruction. The results from this model study illustrate the feasibility of noninvasive estimation of the urethral pressure profile using ultrasound. This offers the prospect of a noninvasive, ultrasound based diagnostic tool for assessment of bladder outlet obstruction in men with lower urinary tract symptoms.

A Role for Peripheral 5-HT2 Receptors in Serotonin-Induced Facilitation of the Expulsion Phase of Ejaculation in Male Rats

The urethrogenital reflex (UGR) is used as a physiological animal model of the autonomic and somatic activity that accompanies ejaculatory-like reflexes (ELRs). Serotonin (5-HT) plays an important role in regulating ejaculation. To examine the effects of intraurethral 5-HT on ELRs and to examine the effects of various 5-HT receptor subtypes on the 5-HT-induced changes in the ELRs. The effects of intraurethral infusion of 5-HT on ELRs were examined by monitoring the urethrogenital reflex in male rats. The effects of various 5-HT receptor-specific antagonists on the 5-HT-induced responses were examined. Main outcome measures were urethral pressure threshold required to elicit the UGR and bulbospongiosus activity or ELRs. Intraurethral infusion of 5-HT (10-1,000 μM) produced a dose-dependent facilitation of the UGR, i.e., decrease in threshold urethral perfusion pressure and an increase in number of ELRs. The 5-HT3 receptor antagonists tropisetron (1 and 3 mg/kg, i.v.) and ramosetron (0.1 and 1 mg/kg, i.v.), the 5-HT7 receptor antagonist SB269970 (3 mg/kg, i.v.), and the 5-HT1 A receptor antagonist WAY-100635 (1 mg/kg, i.v.) all failed to inhibit 5-HT-induced facilitation of the UGR. However, ritanserin (1 mg/kg, i.v.), a nonselective 5-HT2 receptor antagonist, and xylamidine (0.01-1 mg/kg, i.v.), a peripherally restricted nonselective 5-HT2 receptor antagonist, significantly inhibited both the decrease in urethral pressure threshold and the increase in number of ELRs induced by intraurethral infusion of 5-HT. These results suggest that in the male rat urethra, peripheral 5-HT2 receptors are involved in the 5-HT-induced facilitation of the expulsion phase of ejaculation.

Endoscopic Vascular Targeted Photodynamic Therapy with the Photosensitizer WST11 for Benign Prostatic Hyperplasia in the Preclinical Dog Model

Vascular targeted photodynamic therapy with WST11 (TOOKAD® Soluble) is in phase III clinical trials of an interstitial transperineal approach for focal therapy of prostate cancer. We investigated the safety and efficacy of the endourethral route in the context of benign prostatic hyperplasia in the dog model. An optical laser fiber was positioned in the prostatic urethra of 34 dogs, including 4 controls. It was connected to a 753 nm diode laser at 200 mW/cm fluence, delivering 200 to 300 J. WST11 (5 to 15 mg/kg) was infused intravenously in 2 modes, including continuous, starting 5 to 15 minutes before and during illumination, or a bolus 5 to 10 minutes before illumination. Prostate ultrasound, cystourethrogram, urodynamics and histopathology were performed. Followup was 1 week to 1 year. Endourethral WST11 vascular targeted photodynamic therapy was uneventful in all except 1 dog, which experienced urinary retention but reached the 1-week end point. All prostates except those in controls showed hemorrhagic lesions. They consisted of 2 levels of concentric alterations, including periurethral necrosis with endothelial layer destruction and adjacent inflammation/atrophy with normal blood vessels. Prostatic urethral width increased as early as 6 weeks after treatment, while prostatic volume decreased, reaching 25% by 18 to 26 weeks. A parallel decrease in urethral pressure at 6 weeks lasted up to 1 year. We confirmed the vascular effect of endourethral WST11 vascular targeted photodynamic therapy. To our knowledge we report for the first time that the resulting periurethral necrosis led to significant, sustained widening of the prostatic urethra, accompanied by long-term improvement in urodynamic parameters. These findings support future clinical applications of this minimally invasive approach to benign prostatic hyperplasia.

Poster 45: Effectiveness of Botulinum Toxin Injections to the External Sphincter in Treating Incomplete Voiding Postspinal Cord Injury: A Meta-Analysis

Objective: To examine effectiveness of botulinum toxin (BTX) on bladder emptying in individuals with spinal cord injury (SCI). Data Source: Medline, CINAHL, EMBASE, and PsycINFO databases were searched for all relevant articles published between 1980 to March 2010. Study Selection: All trials examining use of BTX injections into the detrusor sphincter in treatment of bladder emptying post-SCI were included if 50% or more of the study sample was comprised of subjects post-SCI and if the SCI sample size was 3 or more. Data Extraction: Studies involved injections of 100–150 units of BTX into 3–4 sites of the detrusor sphincter. A standardized mean difference (SMD) ± SE and 95% confidence interval (CI) was calculated for in each of the studies and the results pooled using a random effects model. Outcomes assessed included postvoid residual urine volume, detrusor pressure, and urethral pressure. Effect sizes were interpreted as: small=0.2, moderate=0.5, large=0.8. Data Synthesis: 5 studies (1 RCT, 4 uncontrolled trials) met inclusion criteria, whereby subjects (pooled total=86) were assessed before and after treatment. Dose of BTX varied among the studies from 300–600 units in total. Significant decrease in postvoid residual urine volume (SMD=1.152±0.261; 95% CI, 0.640–1.665; P=0.0001) and detrusor pressure (SMD=0.865±0.270; 95% CI, 0.336–1.394, P=0.001) was found post-BTX treatment; while no significant decrease in urethral pressure (SMD=1.166; 95% CI, 0.285–1.040, P=0.061) was seen. Conclusions: Results of the meta-analysis indicate BTX is effective in treating bladder voiding dysfunction post-SCI.

Urine leakage related to physical fatigue in women with urinary stress incontinence

To evaluate the frequency of urine leakage related to physical fatigue in women presenting with urinary stress incontinence using a specific questionnaire, and to assess its association with the Bristol Female Lower Urinary Tract Symptoms questionnaire and urodynamic findings. Prospective observational descriptive study. University hospital (urodynamics laboratory). Sixty-one women presenting with urinary stress incontinence and 10 continent women. Not applicable. The participants underwent urethral pressure profile measurement and completed a Bristol Female Lower Urinary Tract Symptoms questionnaire and a specific questionnaire focused on urine leakage related to physical fatigue. Twenty-three (37%) women with urinary stress incontinence claimed to exhibit urine leakage related to physical fatigue more often than one third of the time and 47% claimed to exhibit urinary leakage only after more than one cough. There was a positive correlation between the findings of the specific questionnaire and the presence of a sharp decrease in urethral pressure following repeated cough efforts: question #1 (P = 0.02); question #2 (P = 0.00002); question #3 (P = 0.04). There is a strong association between this questionnaire focused on urine leakage related to fatigue and the presence of a decrease in urethral pressure following repeated coughs.

Decrease in urethral pressure following repeated cough efforts: A new concept for pathophysiology of stress urinary incontinence

To describe the decrease in maximum urethral closure pressure (MUCP) following repeated coughs in women with stress urinary incontinence (SUI). MUCP was recorded at rest and after seven cough efforts in 70 women under age 40 referred for urodynamic investigation (47 women with SUI and 23 women without SUI). The intraclass correlation coefficient for repeatability was very good at 400 mL filling volume: 0.94 (95%CI: 0.85-0.98), as compared to the mean and standard-deviations of the MUCP measurements. A decrease in MUCP >20% after seven cough efforts was observed in 18(38%) patients in the SUI group and in just 1(4%) woman in the non-SUI group (P = 0.0069). Many women with SUI exhibit a sharp decrease in MUCP after repeated coughs. Many hypotheses may explain this phenomenon, including increased fatigue of the periurethral muscles.

Antimuscarinic Drug Inhibits Detrusor Overactivity Induced by Topical Application of Prostaglandin E 2 to the Urethra With a Decrease in Urethral Pressure

Antimuscarinic drugs increase bladder capacity without prominent side effects such as urinary retention even when administered to patients with mild to moderate bladder outlet obstruction. Some mechanisms might exist in the urethra to compensate for the emptying function of the detrusor after the administration of antimuscarinic drugs. We investigated the influence of the antimuscarinic drug propiverine (Taiho Pharmaceutical, Tokyo, Japan) on urethral function. Urethral pressure and rhythmic bladder pressure were simultaneously monitored in urethane anesthetized female Sprague-Dawley rats. Prostaglandin E(2) was continuously administered intravesically or intraurethrally to induce detrusor overactivity. To eliminate the influence of bladder activity and monitor urethral baseline pressure isovolumetric pressure of the urethra was then recorded after cystectomy and ligation of the external urethral meatus. Furthermore, in vitro contractile responses of the urethral circular smooth muscle to field stimulation were examined in the presence of propiverine, tamsulosin (Taiho Pharmaceutical), verapamil, omega-conotoxin and atropine (Sigma). Intravesical or intraurethral administration of prostaglandin E(2) significantly decreased the bladder contraction interval by 10.7% and 36.0%, respectively. Intra-arterial administration of 2 x 10(2) nM/kg propiverine significantly increased the bladder contraction interval in rats receiving intraurethral prostaglandin E(2) by 81.8% but it had no marked effect on rats receiving intravesical prostaglandin E(2). Significant decreases in urethral baseline pressure were found after propiverine administration. Field stimulation induced contraction was inhibited by propiverine and verapamil but not by tamsulosin, omega-conotoxin or atropine. These results suggest that the inhibitory effects of propiverine are more prominent in rats with detrusor overactivity induced by intraurethral prostaglandin E(2) than by intravesical prostaglandin E(2). Propiverine may compensate for detrusor function by decreasing urethral resistance in the voiding phase.

Effects of pregnancy and child birth on urinary symptoms and urodynamics in women with multiple sclerosis

Our objective was to study the impact of pregnancy and delivery on vesicourethral disorders in patients with multiple sclerosis (MS). We performed a retrospective chart review of records of women diagnosed with MS who were referred to the clinic. A total of 102 women with MS (mean age of 44.7 +/- 11.4 years at the time of the study and mean age of 30.0 +/- 9.6 years at the onset of MS) participated in the study. The mean duration of disease was 15 +/- 10 years. The mean Expanded Disability Status Scale score was 5.4 +/- 1.8. For each patient, demographic data, disease characteristics, urological and obstetrical history and urodynamic data were collected. Urinary disorders were classified as irritative (urinary urgency and frequency) or as obstructive (hesitancy of micturition, reduced or interrupted urinary stream and sensation of incomplete bladder emptying). Urodynamic study consisted of cystometry with continuous recording of urethral sphincter electromyography in 77 (76%) cases. Intravesical and intraurethral pressures were recorded. Bladder dysfunctions were classified into neurogenic detrusor overactivity or detrusor underactivity. Pregnancies and deliveries did not influence symptoms. Moreover, the only statistical difference from a urodynamic point of view was a decrease in maximal urethral closure pressure. No interaction between pregnancy, delivery and urinary symptoms was found in this study. The effects of pregnancy and delivery seemed to be the same in women with MS and in healthy women, with a tendency towards a decrease in urethral pressure in women with MS.

Stereotactic electrical stimulation of the pontine micturition centre in the pig

To apply stereotactic electrical stimulation of the pig brainstem and thus identify a pontine micturition centre. In 10 anaesthetized female Vietnamese minipigs a needle-electrode was positioned in the pontine region. Pressure responses in the lower urinary tract identified the micturition centre functionally during electrical stimulation. Stereotactic coordinates were recorded, and the needle visualized by fluoroscopy, magnetic resonance imaging (MRI) or histologically. The stimulation evoked responses similar to voiding, i.e. a urethral pressure decrease followed by a bladder pressure increase; or similar to a continence manoeuvre, i.e. urethral pressure increase and no change in bladder pressure. In a few cases a continence response was evoked by stimulating a site 1 mm away from the site where a voiding response was evoked. The electrode position was detected by the fluoroscopy-based stereotactic procedure followed by subsequent MRI (one animal), and by histological analysis, verifying it to be in the dorsolateral pontine region. These results show that a pontine micturition centre exists in pigs similar to that described in rats, cats, dogs and humans.

Effect of vesical contraction on the non-sphincteric part of the urethra: recognition of vesicourethral inhibitory reflex.

The effect of vesical contraction on the non-sphincteric part of the urethra has been scarcely addressed in the literature. In this study, the hypothesis that detrusor contraction effects dilatation of the non-sphincteric part of the urethra was investigated. Non-sphincteric urethral pressure response to vesical balloon distension with normal saline in increments of 50 mL was recorded in 21 healthy volunteers (mean age 40.7 +/- 10.3 years, 13 men) before and after individual anesthetization of the urethra and urinary bladder. Vesical distension was effected by a 10F balloon-ended catheter introduced into bladder per urethram. Urethral and vesical pressures were measured by means of a two-channel microtip catheter. Small-volume vesical distension effected no significant urethral or vesical pressure changes while distension with 350 and 400 mL of saline produced vesical pressure elevation (P < 0.01) and urethral pressure decrease (P < 0.01). Vesical distension after individual vesical and urethral anesthetization effected no change in the urethral pressure. These results were reproducible. Dilatation of the non-sphincteric part of the urethra upon vesical contraction is suggested to be mediated through a 'vesicourethral inhibitory reflex' and to facilitate passage of urine through the urethra. The reflex may prove to be of diagnostic significance in micturition disorders.

The effect of anterior vaginal wall prolapse on urethral pressure profile.

To evaluate whether anterior vaginal wall prolapse will cause a decrease in urethral pressure. Two hundred ninety-four patients with uterovaginal prolapse served as study cases. In addition, 127 patients without uterovaginal prolapse were included as controls. The urethral pressure profile measurement was performed using a microtransducer and the fluid-bridge method with the patient in the lithotomy position. The parameters of the urethral pressure profile and its associated variables were compared between the control and study groups. The proximal portion of urethral pressure and the resting and stress urethral closure pressures in women with anterior vaginal wall prolapse were significantly lower than those of the control group. An indentation segment (or a plateau pressure zone) in the proximal portion of the urethral pressure profile curve was noted in patients with anterior vaginal wall prolapse, especially for stage I (64.2%) and stage II (73.0%). Anterior vaginal wall prolapse and genuine stress incontinence had a statistically significant odds ratio for predicting the presence of an indentation segment (or a plateau pressure zone) in the proximal portion of the urethral pressure profile curve (1.58 and 3.19, respectively). An indentation segment (or a plateau pressure zone) of the proximal portion of the urethral pressure profile curve was observed in most of our patients with anterior vaginal wall prolapse. Defects in the anterior vaginal wall supports may attenuate the proximal urethral support, and these defects will contribute to a reduction in the proximal urethral pressure.

Dyssynergie vésico-sphinctérienne et toxine botulique

Objective . – Botulinum toxin (BT) injection into the external urethral sphincter is a promising therapy for neurogenic voiding disorders due to detrusor-sphincter dyssynergia (DSD). However the optimal treatment protocol remains unclear. Method. – A PubMed reference search and manual bibliography review were performed, along with a search in the Annales de réadaptation et de médecine physique and in the reports of the International French-language Society of Urodynamics and the International Continence Society, which allowed us to select twelve pertinent articles with PubMed, two articles from the Annales and two conference reports. Our analysis gave special emphasis to assessment criteria, application, dosage and BT injection technique. Results . – Used for the first time in 1988 in spinal cord injury patients to reduce outflow obstruction due to DSD, BT injections have been shown to be a valuable alternative management of bladder dysfunction with DSD. They have been proposed in neurological patients unable to perform self-catheterisation, after drug failure and before surgery. Parameters for results assessment are mostly clinical (increased free interval between voiding, decreased post-void residual urine volumes), urodynamic (improvement in bladder emptying, increase in functional bladder capacity and decrease in urethral pressure) and electromyographic (denervation of striated urethral sphincter). The literature data regarding type of BT, dosage and protocol vary widely. Duration of action is from 2 to 12 months. Both transurethral and transperineal injections monitored by EMG are equally effective in improving detrusor-sphincter dyssynergia. Conclusion . – With few side effects and satisfactory medium-term results, BT should be recommended as a component of DSD therapies. We propose a practical method for BT use.

An investigation of the effects of zaprinast, a PDE inhibitor, on the nitrergic control of the urethra in anaesthetized female rats

1. The effects of L-NAME and zaprinast were investigated (i.v.) on reflex-evoked changes in bladder and urethral pressures in urethane-anaesthetized female rats. 2. L-NAME attenuated reflex-evoked urethral relaxations (65+/-10%), while zaprinast potentiated these responses (68+/-24%). L-NAME and zaprinast also increased baseline urethral pressure and urethral striated muscle (EUS-EMG) activity. These drugs had little effect on the bladder. 3. Following pre-treatment with alpha-bungarotoxin (i.v.) to block urethral striated muscle, L-NAME and zaprinast failed to increase baseline urethral pressure. Further zaprinast failed to alter the size of reflex-evoked urethral relaxations. 4. Intra-urethral zaprinast caused a significant increase while sodium nitroprusside (SNP) and isoprenaline caused decreases in urethral pressure (+14+/-3%, -25+/-5%, -29+/-7%, respectively). These changes were associated with increases in EUS-EMG activity. After chlorisondamine (i.v.), zaprinast caused a significant fall in urethral pressure, while the decrease in urethral pressure caused by SNP and isoprenaline was potentiated. No changes in EUS-EMG activity occurred. 5. These results indicate that a nitrergic pathway mediates reflex-evoked urethral smooth muscle relaxations. The data also indicates that there is a background release of NO, which reduces sphincter skeletal muscle activity. Further, the ability of zaprinast to potentiate nitrergic evoked urethral relaxations involves an increase in striated muscle tone. This appears to be an indirect result of smooth muscle relaxation and is mediated, at least in part, by a chlorisondamine-sensitive mechanism.

Pubovaginal sling procedure for stress incontinence

Urinary stress incontinence associated with poor urethral sphincter function and indicated by a urethral pressure of less than 10 cm. water was treated in 52 cases with a pubovaginal autogenous fascial sling. No urethral sphincter function could be measured in 7 patients. Of these 52 patients 42 had undergone a previous operation for stress incontinence. The uninhibited detrusor dysfunction that accompanied the stress incontinence in 29 cases ceased after operation in 20 but persisted in 9. Postoperative urethral pressure measurements indicated that while the sling increased urethral pressure it did not cause an obstruction during voiding, since there was a measurable decrease in urethral pressure during a detrusor contraction. Urodynamic determinations were useful in patient selection, in the adjustment of sling tension at operation and in the assessment of reasons for failure. A satisfactory result with good urinary control was obtained in 50 cases and the procedure was a failure in 2.

Bladder and urethral responses to pelvic nerve stimulation in the pig.

The aim of our study of the pig was to investigate the responses of smooth muscle of the bladder and the urethral sphincter to preganglionic parasympathetic stimulation, and to assess the effect on the lower urinary tract of IV administration of alpha,beta-methylene-ATP. In seven anaesthetised female pigs, the responses to repeated 20 s pelvic nerve stimulations before and after IV administration of 0.02 mg/kg alpha-beta-methylene-ATP, and the responses to the drug itself, were recorded in the bladder and the urethra separately. In the urethral high-pressure zone, pre-stimulation pressure was a mean of 61+/-11 cmH2O. During pelvic nerve stimulation, urethral pressure declined by 48+/-9 cmH2O, while the bladder pressure increased to 30+/-18 cmH2O. The rate of pressure changes during the first 3 s of stimulation (initiation of voiding) was larger in the urethra than in the bladder (urethral pressure decrease: 13.0+/-3.1 cmH2O/s, bladder pressure increase: 3.2+/-2.5 cmH2O/s). Administration of alpha,beta-methylene-ATP was followed by a significant but temporary enlargement in the bladder response to pelvic nerve stimulation to 36+/-20 cmH2O, p = 0.028, n = 7, but no change in urethral response. At least 80% of the urethral pre-stimulation pressure was exerted by the smooth muscle. The synergic activation of the detrusor and the urethral smooth muscle in response to preganglionic parasympathetic nerve stimulation was controlled by the peripheral nerves or by the neuromuscular transmission. Administration of alpha,beta-methylene-ATP increased the bladder response to pelvic nerve stimulation without changing the urethral response.

Power Doppler of the urethra in continent or incontinent, pre- and postmenopausal women.

Urethral pressure should exceed bladder pressure, both at rest and on stress, for urinary continence to occur. A decrease in urethral pressure is a major factor explaining the pathogenesis of urinary incontinence. A number of elements, such as smooth and striated periurethral muscles, and connective, vascular and elastic tissues, contribute to urethral pressure. The periurethral vessels are influenced by hormonal changes during the menstrual cycle, during pregnancy and postmenopause. We studied the periurethral vessels in 97 women, 57 of whom were incontinent and 40 continent, using power color Doppler velocimetry. The number of periurethral vessels, systolic peak, minimum diastolic values, pulsatility and resistance indexes, as well as systolic-diastolic ratio, were assessed. Statistically significant differences were found between incontinent women in the premenopausal period and those in the postmenopausal period, regarding the number of periurethral vessels, systolic peak, minimum diastolic values, pulsatility and resistance indexes.

The in vivo and in vitro effects of hypoxia on pig urethral smooth muscle.

To assess the in vitro effects of hypoxia on urethral smooth muscle and the role that these may have in the fall in urethral luminal pressure consequent upon interruption of its arterial blood supply. In eight anaesthetized female Large White pigs, femoral blood pressure, urethral luminal pressure and lamina propria blood flow were recorded before, during and after aortic occlusion. In three animals, changes in urethral intramural oxygen tension were also recorded. Smooth muscle strips taken from the mid-urethra were studied in an organ bath under normal and hypoxic conditions, and in the presence of cyanide. The generation of spontaneous tone and the response to electrical-field stimulation were also examined. Urethral luminal pressure declined biphasically after aortic occlusion, from a mean of 83.8 to 39.0 cmH2O. The initial rapid phase seemed to be related to a decrease in urethral lamina propria blood flow, whilst the slower phase appeared to mirror the observed decline in intramural oxygen tension. In vitro, the high spontaneous tone of the muscle strips was abolished by hypoxia or metabolic inhibition whilst the contractile response to nerve stimulation was preserved. The decrease in urethral pressure after aortic occlusion appears to have two components, the first mediated through a decrease in vascular filling of the lamina propria and the second as a result of hypoxia-induced smooth muscle relaxation. The in vitro effects of hypoxia upon urethral smooth muscle concur with the changes observed in vivo.

実験的糖尿病ラットの下部尿路機能に関する研究

Diabetic lower urinary tract disfunction is well known, however, precise mechanism of the lower urinary tract disfunction remains to be solved. The present study is to clarify the lower urinary tract disfunction of diabetic rats by simultaneously measuring bladder and urethral pressures. Female wistar rats were administered with streptozotocin (STZ 65 mg/kg, i.p.) to induce diabetes mellitus. Bladder and urethral pressures during rhythmic bladder contractions were compared under urethane anesthesia (1.0 g/kg, i.v.) between the control rats, diabetic rats, and diuretic rats. The bladder contraction pressures of diabetic rats were decreased initially, but returned to the control values at 8 weeks. Atropine (2.5 mg/kg, i.a.) produced a marked reduction of bladder contraction pressure in the 8 weeks diabetic rats. The diabetic rats showed an increase of urethral pressure simultaneously with an increase of bladder pressure in the initial phase of rhythmic bladder contraction which is totally blocked by striated muscle relaxant. This phenomenon was not observed in the control or diuretic rats. Both group showed an initial decrease of urethral pressure followed by bladder contraction and rhythmic contractions of the urethra. Our results suggest that bladder muscarinic receptors of the 8 weeks diabetic rats are more dominant than those of the other groups, and Mahoney's 4th reflex (urethrosphincteric guarding reflex) is facilitated but Mahoney's 6th reflex (detruthodetrusor facilitative reflex) is suppressed in the diabetic rats. We think that in the diabetic rats, sensory inputs by bladder distension were weak and could not induce Mahoney's 6th reflex until certain threshold values. Diabetic rats might develop changes in the mode of spinal neuronal transmission.

Neural Control of Urethral Outlet Activity in Vivo: Role of Nitric Oxide

The present study investigated the role of nitric oxide (NO) in the reflex changes in urethral outlet activity during micturition. Isovolumetric bladder contractions, urethral pressure and external urethral sphincter electromyogram (EUS EMG) activity were recorded independently in urethane-anesthetized rats. During reflex bladder contractions, the urethra exhibited reflex responses characterized by an initial decrease in urethral pressure in conjunction with a rise in bladder pressure. This was followed by a period of high frequency oscillations (HFOs) associated with maximal urethral relaxation and burst type EUS EMG activity. Administration of N-nitro-L-arginine (L-NOARG) 10 mg./kg. intravenously, a nitric oxide synthase inhibitor, reversibly decreased the magnitude (62 percent, p less than 0.05) and duration (40 percent, p less than 0.05) of reflex urethral relaxation (N = 7). In 4 additional experiments, L-NOARG (10 to 15 mg./kg. intravenously) completely eliminated reflex urethral relaxation during micturition, and this effect was reversed in all animals by the administration of L-arginine (100 to 150 mg./kg. intravenously). Administration of N-nitro-D-arginine (D-NOARG) (10 to 30 mg./kg. intravenously) had no effect on reflex urethral relaxation. Neuromuscular blockade (vecuronium bromide 5 mg./kg. intravenously) reversibly decreased resting urethral pressure and eliminated the HFOs. The urethral smooth muscle relaxation that remained after neuromuscular blockade was eliminated following administration of L-NOARG (10 mg./kg. intravenously) in 2 of 3 animals. These results suggest that reflex urethral responses during micturition involve changes in both smooth and striated muscle activity, and that the predominant neurotransmitter mechanisms that mediate reflex urethral smooth muscle relaxation involve NO.

Urethral pressure variation

Urethral pressure variation (UPV) is a nonpathologic physiological phenomenon. It is found in normal females as well as in females with symptoms from the lower urinary tract. The UPV are caused by activity of urethral smooth and striated muscles. Sometimes only one type of muscle is activated; at other times both types of muscles are activated simultaneously or alternately. Urinary loss in patients with UPV is caused by combined urethral pressure decrease and detrusor pressure increase in most patients. Urinary loss is seldom caused by urethral pressure decrease alone. In 1981 the latter condition was defined by the ICS as the unstable urethra.