Cold stress induces lower urinary tract symptoms

Cold stress as a result of whole-body cooling at low environmental temperatures exacerbates lower urinary tract symptoms, such as urinary urgency, nocturia and residual urine. We established a model system using healthy conscious rats to explore the mechanisms of cold stress-induced detrusor overactivity. In this review, we summarize the basic findings shown by this model. Rats that were quickly transferred from room temperature (27 +/- 2 degrees C) to low temperature (4 +/- 2 degrees C) showed detrusor overactivity including increased basal pressure and decreased voiding interval, micturition volume, and bladder capacity. The cold stress-induced detrusor overactivity is mediated through a resiniferatoxin-sensitve C-fiber sensory nerve pathway involving 1-adrenergic receptors. Transient receptor potential melastatin8 channels, which are sensitive to thermal changes below 25-28 degrees C, also play an important role in mediating the cold stress responses. Additionally, the sympathetic nervous system is associated with transient hypertension and decreases of skin surface temperature that are closely correlated with the detrusor overactivity. With this cold stress model, we showed that 1-adrenergic receptor antagonists have the potential to treat cold stress-exacerbated lower urinary tract symptoms. In addition, we showed that traditional Japanese herbal mixtures composed of Hachimijiogan act, in part, by increasing skin temperature and reducing the number of cold sensitive transient receptor potential melastatin channels in the skin. The effects of herbal mixtures have the potential to treat and/or prevent the exacerbation of lower urinary tract symptoms by providing resistance to the cold stress responses. Our model provides new opportunities for utilizing animal disease models with altered lower urinary tract functions to explore the effects of novel therapeutic drugs.ArticleINTERNATIONAL JOURNAL OF UROLOGY. 20(7):661-669 (2013)journal articl

Advantages of self-tailored mesh for vaginal prolapse

ArticleINTERNATIONAL JOURNAL OF UROLOGY. 19(6):494-495 (2012)journal articl

Expression of α1-Adrenergic Receptor Subtypes and Angiotensin II Type 1 Receptor in the Prostate of Spontaneously Hypertensive Rats

Background :To clarify the mechanisms of lower urinary tract symptoms (LUTS) associated with benign prostate hyperplasia (BPH), we investigated the expression of α1-adrenergic receptor (AR) subtypes and the angiotensin II type 1 receptor (AT1) within the prostate of spontaneously hypertensive rats (SHRs). Methods :Twelve male 25-week-old SHRs and Wistar Kyoto (WKY) rats were randomly separated into two groups (n =6 each). One group was given 20 ml 0.9% sodium chloride solution (saline) orally per kg-body weight daily for one week. The other group received no treatment. After 7 days of saline loading, systolic blood pressure (SBP) and prostate weight were measured. The prostates were immunohistochemically analyzed for α1-AR subtypes and AT1. Results :After 7 days, the SBP and prostate weight of saline-loaded SHRs tended to increase, but was not significantly different compared to the untreated rats.The expression ofα1-AR subtypes and AT1 within the prostates of saline-loaded SHRs was higher than in the untreated ones. In contrast, the expression in the saline-loaded WKY rat prostates did not increase compared to the untreated ones. Conclusion : Increased numbers of α1-AR subtypes and AT1 in saline-loaded SHR prostates might play important roles in the development of LUTS associated with BPH.Article信州医学雑誌. 58(3): 103-114 (2010)journal articl

The Microenvironment of Freeze-Injured Mouse Urinary Bladders Enables Successful Tissue Engineering

Mouse bone marrow-derived cells implanted into freeze-injured bladder walls form smooth muscle layers, but not in intact walls. We determined if the microenvironment within injured urinary bladders was supportive of smooth muscle layer development. The urinary bladders of female nude mice were freeze-injured for 30 s. Three days later, the rate of blood flow in the wounded areas and in comparable areas of intact control urinary bladders was observed by charge-coupled device (CCD) video microscopy. Injured and control bladder walls were also analyzed histologically and cytologically. Growth factor mRNA expression was determined by real-time reverse transcription polymerase chain reaction arrays. The injured regions maintained a partial microcirculation in which blood flow velocity was significantly less than in controls. The injured bladder walls had few typical smooth muscle layers, and blood vessels in the walls had reduced smooth muscle content. The loss of smooth muscle cells in the bladder walls may have resulted in the formation of large porous spaces seen by scanning electron microscopy of the injured areas. The expression of nineteen growth-related mRNAs, including secreted phosphoprotein 1, inhibin beta-A, glial cell line-derived neurotrophic factor, and transforming growth factor beta 1, were significantly upregulated in the injured urinary bladders. In conclusion, the microenvironment in freeze-injured urinary bladders enables successful tissue engineering.ArticleTISSUE ENGINEERING PART A. 15(11):3367-3375 (2009)journal articl

Male lower urinary tract symptoms and a1D-adrenoceptors

Historically, a1-adrenoceptors have been classified into three subtypes (a1A, a1B and a1D) that are widely distributed in various organs. Research on the a1D-adrenoceptors in the bladder, urethra and prostate has focused on the relationship between expression levels and symptoms of bladder outlet obstruction, and the implications and functional roles of a1D-adrenoceptors subtypes in these organs. The a1D-adrenoceptor messenger ribonucleic acid and protein seem to be increased in obstructed bladders or small capacity bladders. In contrast, a1D-adrenoceptor subtype knock-out mice have been found to have a prolonged voiding interval. Interestingly, an a1D-adrenoceptor antagonist was found to inhibit the facilitation of afferent nerve activity for the micturition reflex induced by intravesical infusion of acetic acid. Clinically, patients who felt urgency at low filling volumes and had a small bladder capacity were found to have more a1D-adrenoceptor messenger ribonucleic acid in their bladder mucosa than patients who felt urgency at high filling volumes and had a large bladder capacity. An a1D-adrenoceptor antagonist was found to increase the first desired volume and the maximum desired volume while decreasing detrusor overactivity in pressure flow studies. Thus, a1D-adrenoceptors in the lower urinary tract might play an important role in the pathophysiology of lower urinary tract disorders.ArticleINTERNATIONAL JOURNAL OF UROLOGY. 20(1):73-78 (2013)journal articl

Bone Marrow-Derived Cells Implanted into Radiation-Injured Urinary Bladders Reconstruct Functional Bladder Tissues in Rats

The purpose of this study was to determine whether bone marrow-derived cells implanted into radiation-injured urinary bladders could reconstruct functional bladder tissues. The pelvic region of anesthetized female Sprague-Dawley (SD) rats was irradiated with 2 Gy once a week for 5 weeks. After the last irradiation, the rats were maintained for 2 weeks. Bone marrow cells were harvested from the femurs of donor male green fluorescence protein (GFP)-transfected SD rats and cultured for 7 days. Two weeks after the last radiation exposure, the cultured adherent, proliferating bone marrow-derived cells were implanted into the walls of irradiated urinary bladders. For controls, cell-free solutions were similarly injected. Four weeks after donor cell or control implantations, cystometric, histological, and immunohistochemical investigations were performed. Two weeks after the last irradiation, the smooth muscle layers and nerve fibers of the irradiated urinary bladders were disorganized. The proportions of smooth muscle layer and nerve fiber areas were significantly decreased compared with sham-irradiated urinary bladders. In addition, the remaining smooth muscle cells within the irradiated urinary bladders expressed P4HB, an indicator of collagen synthesis. In the cystometric investigations, the voiding interval of irradiated rats was irregularly prolonged, 7.92 +/- 1.09 min, and the residual volume, 0.13 +/- 0.03 mL, was significantly higher compared with the sham-irradiated rats (5.50 +/- 0.43mL and 0.05 +/- 0.01 mL). After 4 weeks, the smooth muscle layers and nerve fibers in the cell-free control urinary bladders remained similar to the pre-implanted irradiated urinary bladders; however, the cell-implanted urinary bladders contained reconstructed smooth muscle layers and nerve fibers, the proportions of each were significantly higher than those in the cell-free injected controls. The expression of P4HB within the cell-implanted urinary bladders decreased. Some GFP-positive implanted cells differentiated into smooth muscle-and nerve-like cells and became organized into the reconstructed tissues. The voiding interval of the cell-implanted rats, 5.46 +/- 0.33 min, was regular and similar to that of the sham-irradiated rats, and significantly less than that of the cell-free injected controls, 7.39 +/- 0.54 min. The residual volume, 0.04 +/- 0.01 mL, was similar to that of the sham-irradiated rats and significantly decreased compared with that of the cell-free injected controls, 0.15 +/- 0.05 mL. Therefore, the implantation of bone marrow-derived cells is a potentially useful treatment for radiotherapy-induced urinary dysfunctions.ArticleTISSUE ENGINEERING PART A. 18(15-16):1698-1709 (2012)journal articl