Scrotal lymphangioma in a middle-aged man.

Scrotal lymphangioma is a rare, acquired, idiopathic conditions. Surgical resection can result in successful outcomes. A 43-year-old man presented with a painless scrotal mass. Ultrasonography and magnetic resonance imaging revealed a multifocal cystic mass in the scrotum that showed partial hypervascularity without connection to the skin. We performed complete surgical resection of the mass and histopathologically diagnosed the patient with lymphangioma. Acquired scrotal lymphangiomas are rare. Moreover, there was no apparent cause, such as injury; thus, this case was considered idiopathic. Complete surgical resection led to a successful resolution.

Efficacy of Combination Treatment with Tadalafil and Mirabegron in Patients with Benign Prostatic Hyperplasia Who Presented with Persistent Storage Symptoms After Tadalafil Monotreatment: A Prospective, Multicenter, Open-Labeled Study.

Background: The aim of this study is to evaluate the efficacy and safety of tadalafil, a phosphodiesterase type 5 inhibitor, plus mirabegron, a ß3-adrenoreceptor agonist, in patients with benign prostatic hyperplasia who presented with persistent storage symptoms after tadalafil monotreatment. Methods: The registration of this study started in August 2016 and ended in July 2019. The inclusion criteria included patients aged ≥ 50 years who were diagnosed with benign prostatic hyperplasia and who presented with overactive bladder symptoms. Patients were treated with oral tadalafil 5 mg once daily for 4 weeks. Then, its efficacy was evaluated. Patients who responded to the treatment received oral tadalafil 5 mg once daily for 4 more weeks (monotreatment group). Meanwhile, those who did not respond received oral tadalafil 5 mg and mirabegron 50 mg, which is an add-on treatment, once daily for 4 more weeks (combination therapy group). Results: After 8 weeks, the monotreatment group (n = 19) and the combination group (n = 56) had significantly better total Overactive Bladder Symptom Score and International Prostate Symptom Score and International Prostate Symptom Score voiding and storage subscale scores. Moreover, the two groups experienced significant improvements in the total Overactive Bladder Questionnaire and Nocturia Quality of Life Questionnaire scores, and Nocturia Quality of Life Questionnaire Bother/Concern subscale score after 8 weeks. However, there were no cases of urinary retention or serious adverse events. Conclusion: Combination treatment with tadalafil and mirabegron is effective and safe for patients with benign prostatic hyperplasia who presented with persistent storage symptoms after tadalafil monotreatment. Hence, tadalafil plus mirabegron is a promising therapeutic option, and it can improve overactive bladder related-quality of life.

Incidence and predictive factors of orgasmic dysfunction after robot-assisted radical prostatectomy: A cross-sectional, questionnaire-based study.

OBJECTIVE: We sought to evaluate the incidence and extent of orgasmic dysfunction in patients after robot-assisted radical prostatectomy and to identify factors that could predict patients at risk. METHODS: A single-center, questionnaire-based, cross-sectional study was conducted on patients who underwent robot-assisted radical prostatectomy (n = 523) between October 2010 and November 2019. In addition to six questions about sexual activity, orgasmic function, altered perception of orgasms, dysorgasmia, and climacturia, the International Consultation on Incontinence Questionnaire Short Form was administered. In February 2020, a letter was mailed inviting patients to participate in the survey. The primary outcome measure was the rate of orgasmic dysfunction. Logistic regression analyses were used to identify predictors of orgasmic dysfunction. RESULTS: Overall, 259 questionnaires were used for analysis. Among sexually active patients (n = 145), 33 (22.8%) reported anorgasmia, and 83 (57.2%) reported decreased orgasm intensity. Twenty-two (15.1%) patients reported dysorgasmia; among these patients, the pain was experienced almost always or always in 13.6%, sometimes in 13.6%, and a few times in 72.8% of cases. Climacturia was reported by 44 patients (30.3%). Nerve-sparing procedures decreased the risk of anorgasmia (odds ratio 0.37, 95% confidence interval 0.15-0.88) and urinary incontinence increased the risk of climacturia (odds ratio 3.13, 95% confidence interval 1.20-8.15). CONCLUSIONS: These results indicate that orgasmic dysfunction after robot-assisted radical prostatectomy is relatively common.

Extent of pelvic lymph node dissection improves early oncological outcomes for patients with high-risk prostate cancer without lymph node involvement after robot-assisted radical prostatectomy.

BACKGROUND: We investigated the effect of the extent of pelvic lymph node dissection (LND) on biochemical recurrence (BCR) in patients with prostate cancer (PCa) without lymph node involvement (LNI) treated with robot-assisted radical prostatectomy (RARP). METHODS: We retrospectively analyzed data from 378 patients who underwent RARP with LND at our hospital between October 2010 and June 2019. The BCR-free survival rate was determined using Kaplan-Meier analysis, and Cox regression analysis was used to investigate BCR prognostic factors. The total score calculated from the D'Amico risk classification and the percentage of positive biopsy cores were used for analysis. Patients were classified into 3 BCR risk groups (low risk: 0-3 points, intermediate risk: 4-5 points, and high risk: 6-8 points). RESULTS: Limited LND was performed in 161 patients (42.6%), extended LND in 217 patients (57.4%), and BCR was confirmed in 66 patients (17.5%) after RARP. Both univariate and multivariate analyses showed no significant difference in the association between the extent of LND and BCR. The Kaplan-Meier curve for BCR generated using our risk classification for patients with PCa without LNI showed no significant association between the extent of LND and BCR in the low-risk group (p = 0.790). A significantly improved BCR-free survival was observed in the extended LND group among patients with PCa at intermediate risk or higher (p < 0.05). CONCLUSION: According to our risk classification, BCR may be less likely to occur when extended LND is performed during RARP for patients with localized PCa at intermediate risk or higher.

Sarcopenia is associated with survival in patients with urothelial carcinoma treated with systemic chemotherapy.

BACKGROUND: Sarcopenia impacts perioperative outcomes and prognosis in various carcinomas. We aimed to investigate whether sarcopenia at the time of chemotherapy induction in patients with urothelial carcinoma is associated with prognosis. METHODS: We evaluated patients treated with chemotherapy for urothelial carcinoma between April 2013 and February 2018 at our institution and affiliated centers. Skeletal muscle mass (total psoas muscle, paraspinal muscle, and total skeletal muscle areas) were used to calculate the total psoas muscle index, paraspinal muscle index, and skeletal muscle index. All participants were grouped as per cutoff points set at the median value for each sex. Overall survival was evaluated using Cox regression analysis. RESULTS: Of the 240 patients, 171 were men and 69 were women; mean age during chemotherapy was 71 years (range: 43-88); and 36, 56, and 148 patients were at stages II, III, and IV, respectively. Paraspinal muscle index was most associated with the prognosis; groups with lower paraspinal muscle index were defined as sarcopenic (men: ≤ 20.9 cm2/m2, women: ≤ 16.8 cm2/m2). The overall survival was significantly longer in the non-sarcopenia group including all stages (p = 0.001), and in stage III (p = 0.048) and IV (p = 0.005) patients. There was no significant difference among stage II patients (p = 0.648). After propensity score matching, survival was still significantly longer in the non-sarcopenia group (p = 0.004). CONCLUSIONS: Paraspinal muscle index measurements obtained during chemotherapy induction for urothelial carcinoma were independent prognostic factors. The absence of sarcopenia may lead to long-term survival in patients undergoing chemotherapy for urothelial carcinoma.

Longitudinal, 5-year long-term outcomes for urinary continence and quality of life after robot-assisted radical prostatectomy in Japanese patients.

OBJECTIVES: The aim of this study was to investigate the longitudinal 5-year long-term outcomes for urinary continence and quality of life (QOL) after robot-assisted radical prostatectomy (RARP), particularly nerve-sparing. METHODS: Among patients who underwent RARP between October 2010 and October 2015, postoperative urinary symptoms were retrospectively examined using the International Prostate Symptom Score (IPSS), International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF), QOL index, and number of pads used. Patients were divided into nerve-sparing and non-nerve-sparing groups, and all data were evaluated before and at 1, 3, 6, 12, 24, 36, 48, and 60 months after surgery. RESULTS: After propensity score matching, 47 patients each were included in the two groups. No significant difference in the IPSS or QOL index was seen between groups. The IPSS and QOL index showed an increase in the first month after RARP, but at 6 months, values were lower than preoperative levels and then slowly improved. Pad-free rates at 5 years after surgery were 93.6% and 80.1% in the nerve-sparing and non-nerve-sparing groups, respectively (P = .029). ICIQ-SF scores were significantly improved in the nerve-sparing compared with the non-nerve-sparing group at 1, 3, and 6 months after surgery. After 12 months, no significant changes were identified until 60 months. CONCLUSIONS: In this study, nerve-sparing had a strong impact on urinary continence in the early postoperative period. After 12 months, urinary continence remained stable until 60 months.

Response to Platinum-based Chemotherapy Rechallenge for Patients With Pembrolizumab-refractory Urothelial Carcinoma.

BACKGROUND: This study aimed to investigate the response to platinum-based chemotherapy rechallenge in patients with pembrolizumab-refractory urothelial carcinoma. PATIENTS AND METHODS: We retrospectively reviewed 14 patients with pembrolizumab-refractory urothelial carcinoma. Each patient received a regimen that they had not previously received (paclitaxel plus carboplatin in 10, gemcitabine plus docetaxel and carboplatin in four). Tumor response and adverse events were assessed. We evaluated overall survival from the chemotherapy rechallenge start date until death. RESULTS: The median overall survival was 11.2 months. The disease-control rate was 85.7%. Partial responses occurred in the metastases in lymph nodes in three (37.5%) patients, lung in one (25%), peritoneal in three (75%), and liver in three (100%). Neutropenia of grade ≥3 occurred in 13 (92.9%) patients. CONCLUSION: The activity of platinum-based chemotherapy rechallenge after pembrolizumab was maintained. Neutropenia was observed in most patients.

Efficacy of Combination Chemotherapy With Docetaxel, Estramustine and Carboplatin in Men With Castration-resistant Prostate Cancer.

Background: The efficacy of docetaxel and carboplatin with oral estramustine was evaluated in patients with castration-resistant prostate cancer. Patients and Methods: Patients were treated with intravenous docetaxel at 30 mg/m2 on days 1, 8, 15, and 22 of a 28-day cycle. Intravenous carboplatin (area under the curve, 6 mg/ml/min) was administered on day 1. Patients received oral estramustine at 626.8 mg/day throughout the treatment protocol. Patients were evaluated for response, with treatment continued until cancer progression or onset of severe adverse events. Results: Twenty patients with castration-resistant prostate cancer were treated for a median of 3.5 cycles. Prostate-specific antigen decreased by more than 30% in 18 patients, including 14 patients with a decrease of more than 50%. Median overall survival was 11 months, prostate-specific antigen progression-free survival was 6.5 months, and radiographic progression-free survival was 7 months. Conclusion: Docetaxel and carboplatin with oral estramustine shows efficacy against castration-resistant prostate cancer.

Evaluation of a Program of Clean Intermittent Catheterization for Underactive Bladder After Radical Hysterectomy.

BACKGROUND: Dysfunction of the lower urinary tract is the most common complication of radical hysterectomy (RH). However, there are no established treatment protocols for postoperative underactive bladder (PUB). We developed our own new program for the treatment of underactive bladder (UB) after RH and evaluated it retrospectively. METHODS: In this program, there are five steps for patients to follow according to their urinary condition. The first step is the administration of urapidil 30 mg, voiding six times at a predetermined time each day, and clean intermittent catheterization (CIC) after each voiding. As the patient's condition improves, the number of CICs is reduced, and the medication is stopped. The last step includes voiding six times at a predetermined time each day. When the volume of residual urine (RU) is less than 100 mL, patients move on to the next step. When the volume of RU exceeds 100 mL, patients return to the previous step. RESULTS: Of the 75 patients who visited our department, 41 were eligible for this program. Twenty-two patients visited our department because of urinary retention (UR), and 19 patients were admitted because of increased RU. The mean RU volume was 276.3 mL (range, 150-550 mL). After completing the program, 39 (95.1%) patients no longer required CIC. The mean time to withdrawal of CIC was 25.1 weeks (range, 1-72 weeks). Thirty-six patients no longer required medical treatment, including urapidil, for PUB. Of the 5 patients who had persistent PUB after treatment, 2 patients continued CIC and urapidil, and three patients continued urapidil alone. CONCLUSION: The present results demonstrate that the program of CIC in combination with urapidil is effective for the management of PUB after RH.

Evaluation of Incontinence after Robot-Assisted Laparoscopic Radical Prostatectomy: Using the International Consultation on Incontinence Modular Questionnaire Short Form and Noting the Number of Safety Pads Needed by Japanese Patients.

BACKGROUND: The definition of continence after robot-assisted laparoscopic radical prostatectomy (RARP) has not been consistently defined, with many studies only noting the amount of safety pads used. We therefore examined what definition of continence would be appropriate, employing both the International Consultation on Incontinence Modular Questionnaire Short Form (ICIQ-SF) and the number of pads used by patients. We also evaluated the relationship between the number of pads used and degree of incontinence. METHODS: Patients who underwent RARP between October 2010 and July 2014 in our department were included in the present study. All patients were evaluated by ICIQ-SF and the number of pads used 1, 3, 6 and 12 months after surgery. Frequency of incontinence and amount of incontinence were evaluated by ICIQ-SF Questions 1 and 2 respectively at 12 months. Quality of life (QOL) was evaluated by ICIQ-SF Question 3 at 1, 3, 6, and 12 months after RARP. RESULTS: The overall study population was 156 patients. In Question 1, 19 patients answered that they leaked urine several times a day, but 5 patients did not use pads, and 8 patients were using only 1 pad a day. In Question 2, 8 patients answered that they leaked a moderate amount of urine, but 2 patients did not use any pads, and 3 patients used only 1 pad a day. QOL showed significant differences between using no pad, 1 pad, or ≥ 2 pads at 1, 3, 6, and 12 months after RARP. CONCLUSION: Simply noting the number of pads used by a patient is an insufficient way to evaluate incontinence after RARP. Assessment by an appropriate questionnaire is also needed.

Impact of postoperative phosphodiesterase type 5 inhibitor treatment on lower urinary tract symptoms after robot-assisted radical prostatectomy: a longitudinal study.

OBJECTIVE: This study aimed to assess the role of tadalafil, a phosphodiesterase type 5 inhibitor (PDE5-I), in recovery of lower urinary tract symptoms (LUTS) after robot-assisted radical prostatectomy (RARP). MATERIALS AND METHODS: All patients treated with RARP between October 2010 and August 2013 were enrolled in this retrospective study on prospectively collected data. Patients were retrospectively divided into groups according to postoperative treatment: patients taking tadalafil twice weekly from 1 month to 6 months after RARP, and patients not taking tadalafil. The International Prostate Symptom Score (IPSS), the Overactive Bladder Symptom Score (OABSS) and urinary continence (UC) were assessed preoperatively (2 days before RARP) and at 1, 3, 6, 9 and 12 months after RARP. RESULTS: There was no difference in the overall IPSS score between the groups. At 6 and 9 months, the IPSS storage symptom scores were significantly lower in patients taking tadalafil than in patients not taking tadalafil. In patients with overactive bladder (OAB) before RARP (n = 22), no differences in the total scores of OABSS were seen between patients taking tadalafil and patients not taking tadalafil. On the other hand, in non-OAB patients before RARP (n = 68), at 3, 6 and 9 months, the total scores of OABSS were significantly lower in patients taking tadalafil than in patients not taking tadalafil. No differences in UC rates after surgery were seen between the groups. CONCLUSION: Postoperative tadalafil treatment may be temporarily effective for the recovery of the IPSS storage symptom scores and OABSS.

Impact of antioxidants on seminal vesicles function and fertilizing potential in diabetic rats.

Diabetes mellitus significantly affects the male reproduction and sexual function. In the present study, we investigated the diabetes-induced dysfunction of seminal vesicles (SVs) in the diabetes-rat model and the role of antioxidants. Streptozotocin-induced diabetes after 4 weeks caused smaller size of the organs, hypercontractility, histological abnormalities, increased concentrations of malondialdehyde in the serum and tissue, overexpression of oxidative stress markers, and cleaved caspase-3 as identified by immunohistochemistry in the SVs. In addition, diabetes resulted in deceased levels of serum testosterone and no newborns after the mating studies. Antioxidants significantly normalized all the above parameters, except for the severely decreased serum testosterone levels and the negative outcome of the mating studies. The present study gives evidence for the important role of diabetes-induced oxidative stress in the function and structure of these androgen-dependent organs. Antioxidants may be a promising supplementary therapy for diabetic male patients to alleviate ejaculatory disorders but alone is not efficient treatment for the mitigation of infertility.

A prognostic model for predicting urinary incontinence after robot-assisted radical prostatectomy.

BACKGROUND: The aim of this study is to develop a novel prognostic model for estimating the risk of postoperative urinary incontinence (UI) after robot-assisted radical prostatectomy (RARP). METHODS: Participants comprised 131 men who underwent RARP at our hospital from 2011 to 2013. Cox regression analyses were performed to evaluate associations between UI and preoperative factors including filling cystometry and pressure-flow study results and magnetic resonance imaging. RESULTS: Logistic regression analyses revealed significant associations between membranous urethral length or levator thickness and UI at 3 and 6 months. Stratification produced high (membranous urethral length < 9.5 mm or levator thickness < 9.0 mm) and low (membranous urethral length ≥ 9.5 mm and levator thickness ≥ 9.0 mm) UI risk groups. These inter-group differences in UI rate were significant. CONCLUSIONS: We developed a novel prognostic model based on preoperative patient data that can be used for patient counselling.

Urothelial Carcinoma Recurrence at an Ileal Orthotopic Neobladder and Unilateral Lower Ureter After Surgery.

The recurrence of urothelial carcinoma in an orthotopic neobladder is rare. We report the case of a 61-year-old man with a muscle-invasive bladder tumor that was treated using radical cystectomy and the creation of a Studer's orthotopic neobladder. However, nine years after the cystectomy, we detected a mass at the left ureteroileal anastomosis. We successfully performed Studer's neobladder resection, urethrectomy, and left nephroureterectomy to remove the entire mass. Pathological examination revealed urothelial carcinoma with adenocarcinoma in the neobladder and adenocarcinomatous metastasis in the mesenteric lymph node.

Anandamide transporter-mediated regulation of the micturition reflex in urethane-anesthetized rats.

PURPOSE: The aim of this study was to investigate the effects of an anandamide transporter inhibitor that can increase endogenous anandamide concentration on the micturition reflex in urethane-anesthetized rats. METHODS: Continuous cystometrograms were performed in female Sprague-Dawley rats under urethane anesthesia. After stable micturition cycles were established, VDM11 (1, 3 and 10 mg/kg), an anandamide membrane transporter inhibitor, was administered intravenously to evaluate changes in bladder activity. In experiments examining the effects of cannabinoid (CB) receptor antagonists, VDM11 (10 mg/kg) was injected intravenously when the first bladder contraction was observed after intravenous administration of AM251, a CB1 receptor antagonist (3 mg/kg), or AM630, a CB2 receptor antagonist (3 mg/kg). RESULTS: Intravenous administration of VDM11 increased intercontraction intervals and threshold pressure at doses of 3 mg/kg or higher in dose-dependent fashion. When AM251 was administered one voiding cycle before VDM11 administration, the increases in intercontraction intervals and threshold pressure induced by VDM11 administration alone were not seen. In contrast, when AM630 was administered before VDM11 administration, increases in intercontraction intervals and threshold pressure were observed, as they were after VDM11 alone. CONCLUSION: These results suggest that anandamide, an endogenous CB ligand, can modulate the micturition reflex and that anandamide transporters play an important role in this modulation. In urethane-anesthetized rats, inhibition of the uptake of anandamide can inhibit the micturition reflex and these inhibitory effects of VDM11 are at least in part mediated by the CB1 receptor.

Angiotensin II centrally induces frequent detrusor contractility of the bladder by acting on brain angiotensin II type 1 receptors in rats.

Angiotensin (Ang) II plays an important role in the brain as a neurotransmitter and is involved in psychological stress reactions, for example through activation of the sympatho-adrenomedullary system. We investigated the effects of centrally administered Ang II on the micturition reflex, which is potentially affected by the sympatho-adrenomedullary system, and brain Ang II receptors in urethane-anesthetized (1.0 g/kg, intraperitoneally) male rats. Central administration of Ang II (0.01, 0.02, and 0.07 nmol per rat, intracerebroventricularly, icv) but not vehicle rapidly and dose-dependently decreased the urinary bladder intercontraction interval, without altering the bladder detrusor pressure. Central administration of antagonists of Ang II type 1 but not type 2 receptors inhibited the Ang II-induced shortening of intercontraction intervals. Administration of the highest dose of Ang II (0.07 nmol per rat, icv) but not lower doses (0.01 and 0.02 nmol per rat, icv) elevated the plasma concentration of adrenaline. Bilateral adrenalectomy reduced Ang II-induced elevation in adrenaline, but had no effect on the Ang II-induced shortening of the intercontraction interval. These data suggest that central administration of Ang II increases urinary frequency by acting on brain Ang II type 1 receptors, independent of activation of the sympatho-adrenomedullary system.

Spinal glycine transporter-1 inhibition influences the micturition reflex in urethane-anesthetized rats.

PURPOSE: Glycine is an inhibitory neurotransmitter in the central nervous system. So far, two types of glycine transporters (GlyTs), GlyT-1 and GlyT-2, have been cloned. The aim of this study is to investigate the effects of a selective GlyT-1 inhibitor that can increase endogenous glycine concentration on the micturition reflex in urethane-anesthetized rats. METHODS: Continuous cystometrograms (0.04 ml/min) were performed in female Sprague-Dawley rats (232-265 g) under urethane anesthesia. After stable micturition cycles were established, ALX5407, a selective GlyT-1 inhibitor, was administered intrathecally or intracerebroventricularly to evaluate changes in bladder activity. Cystometric parameters were recorded and compared before and after drug administration. RESULTS: Intrathecal administration of ALX5407 (1, 3, 10 and 30 µg) increased intercontraction intervals at doses of 3 µg or higher in a dose-dependent fashion. Intrathecal administration of ALX5407 (1, 3, 10 and 30 µg) also increased pressure threshold at doses of 3 µg or higher in a dose-dependent fashion. However, when ALX5407 (1, 3, 10 and 30 µg) was administered intracerebroventricularly, there were no significant changes in intercontraction intervals, pressure threshold, maximum voiding pressure or baseline pressure or post-void residual urine volume at any doses tested. CONCLUSION: The results of our study indicate that GlyT-1 plays an important role in the modulation of micturition. Furthermore, these findings indicate that in urethane-anesthetized rats suppression of GlyT-1 can inhibit the micturition reflex at the spinal cord level. Thus, GlyT-1 could be a potential target for the treatment of bladder dysfunction such as overactive bladder.

Comparison of the overactive bladder symptom score and the overactive bladder symptom score derived from the bladder diaries.

AIMS: The overactive bladder symptom score (OABSS) is a useful tool for assessing the four key symptoms of overactive bladder (OAB), but it sometimes misrepresents a patient's actual voiding status. To examine whether the patient-determined OABSS underestimates or overestimates the true status, its results were compared to those of the OABSS derived from a 7-day bladder diary (OABSS-BD). METHODS: Records of patients who visited our outpatient clinic with lower urinary tract symptoms were evaluated retrospectively. The patients were asked to complete the OABSS and the 7-day bladder diary (BD). The OABSS-BD was created from the 7-day BD. Questions were compared between the OABSS and the OABSS-BD. RESULTS: A total of 44 men and 31 women were evaluated. For daytime frequency, the mean OABSS score was 1.03 ± 0.57 and the OABSS-BD score was 0.69 ± 0.52 (P < 0.01). For nighttime frequency, the mean OABSS score was 2.27 ± 0.84, and the OABSS-BD score was 1.96 ± 1.00 (P = 0.04). For urinary urgency, the mean OABSS score was 2.49 ± 1.83, and the OABSS-BD score was 2.70 ± 1.90 (P = 0.27). For urgency incontinence, the mean OABSS score was 1.67 ± 1.92, and the OABSS-BD score was 1.52 ± 1.87 (P = 0.28). For the total score, the mean OABSS total score was 7.26 ± 3.92, and the OABSS-BD score was 6.98 ± 3.26 (P = 0.23). CONCLUSIONS: The OABSS is a very simple and useful tool. However, compared to the results from the 7-day FVC, the present patients overestimated daytime and nighttime frequency.

Vesicovascular reflexes in the spontaneously hypertensive rat.

AIMS: We investigated the effects of hypertension and acute blood pressure changes on rats' vesicovascular reflexes (VVRs). MAIN METHODS: Twelve-week-old male Wistar rats and spontaneously hypertensive rats (SHRs) were anesthetized with urethane, and underwent real-time cystometry and blood pressure monitoring. The SHRs were administered nifedipine or valsartan intravenously. The Wistar rats were administered intravenous noradrenaline continuously. The intercontraction intervals, maximum detrusor pressures, blood pressure during the voiding and the urine storage phases, blood pressure elevations associated with the VVRs, and arterial pulses were assessed. Plasma adrenaline and noradrenaline concentrations were measured using HPLC. The degree of atherosclerosis was assessed histologically based on the aortic wall thickness. KEY FINDINGS: Blood pressure elevations associated with the voiding reflexes were significantly lower and intercontraction intervals were significantly shorter in the SHRs compared with the Wistar rats. Although nifedipine and valsartan reduced the systolic blood pressure and noradrenaline increased the systolic blood pressure, they failed to alter the blood pressure elevations associated with the VVRs and the intercontraction intervals. No significant differences occurred with respect to the maximum detrusor pressures among the experimental groups. The reflected waves' shapes were normal in the Wistar rats, but they almost disappeared in the SHRs. The aortic walls were significantly thicker in SHRs compared with those in Wistar rats. SIGNIFICANCE: The blood pressure elevations associated with the VVRs were lower in the SHRs than in the Wistar rats. Acute blood pressure reductions failed to ameliorate the blood pressure elevations associated with VVRs in the SHRs.

Effects of sensory neuron-specific receptor agonist on bladder function in a rat model of cystitis induced by cyclophosphamide.

PURPOSE: To investigate the effects of activation of sensory neuron-specific receptors (SNSRs) on cyclophosphamide (CYP) bladder overactivity in rats. METHODS: Female Sprague-Dawley rats (235-258 g) were used. Rats were injected with either CYP (200 mg/kg, intraperitoneally) or saline (control). Continuous cystometrograms (0.04 ml/min) were recorded 48 h after CYP or saline injection under urethane anesthesia. After stable micturition cycles were established, a selective rat SNSR1 agonist, bovine adrenal medulla 8-22 (BAM8-22), was administered intravenously or intrathecally. RESULTS: Cyclophosphamide treatment-induced higher baseline pressure and shorter intercontraction intervals compared with the control group. Intravenous administration of BAM8-22 at 10, 30 and 100 µg/kg significantly increased intercontraction intervals in the CYP-treated group. Intrathecal administration of BAM8-22 at 0.03, 0.1 and 0.3 µg also significantly increased intercontraction intervals in the CYP-treated group. Intravenous or intrathecal administration of BAM8-22 did not change baseline pressure or maximum voiding pressure in the CYP-treated group. CONCLUSIONS: These findings indicate that activation of SNSRs can suppress CYP-induced bladder overactivity, probably due to suppression of bladder afferent activity.