Activity Of Lower Urinary Tract Research Articles

Effects of a new selective β3 -adrenoceptor agonist, vibegron, on bladder and urethral function in a rat model of Parkinson's disease.

Parkinson's disease caused by the loss of dopaminergic neurons induces not only motor dysfunction but also lower urinary tract dysfunction. Patients with Parkinson's disease have recently been reported to experience both urge urinary incontinence (overactive bladder) and stress urinary incontinence, the latter of which occurs when the pressure of the bladder exceeds that of the urethra. Vibegron is a highly selective novel β3 -adrenoceptor agonist approved for the treatment of overactive bladder. However, how β3 -adrenoceptor agonists affect urethral function remains unclear. In a clinical report, the urethral function of patients with Parkinson's disease was shown to be degraded. The present study aimed to investigate the effects of vibegron on lower urinary tract activity in a rat model of Parkinson's disease. In a rat model of Parkinson's disease induced by unilateral 6-hydroxydopamine injection into the substantia nigra pars compacta, we examined the effects of vibegron on bladder and urethral activity. Cystometric analysis revealed that, compared with vehicle injection, intravenous injection of 3 mg/kg vibegron significantly increased the inter-contraction interval (p < .05) and reduced voiding pressure (p < .01). However, no significant effects on urethral function were observed. The results of the present study provide corroborating evidence that bladder dysfunction is suppressed by the administration of vibegron in Parkinson's disease model rats, confirming that vibegron is effective for treating overactive bladder without further worsening urethral function. These findings may contribute to a better understanding of the mechanisms of β3 -adrenoceptor agonists.

MP17-01 ACID-SENSING ION CHANNELS ARE INVOLVED IN AFFERENT EXCITATORY TRANSMISSION CONTROLLING REFLEX BLADDER ACTIVITY IN MICE

You have accessJournal of UrologyBladder & Urethra: Anatomy, Physiology & Pharmacology1 Apr 2014MP17-01 ACID-SENSING ION CHANNELS ARE INVOLVED IN AFFERENT EXCITATORY TRANSMISSION CONTROLLING REFLEX BLADDER ACTIVITY IN MICE Mitsuharu Yoshiyama, Hideki Kobayashi, Isao Araki, and Masayuki Takeda Mitsuharu YoshiyamaMitsuharu Yoshiyama More articles by this author , Hideki KobayashiHideki Kobayashi More articles by this author , Isao ArakiIsao Araki More articles by this author , and Masayuki TakedaMasayuki Takeda More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2014.02.522AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Acid-sensing ion channels (ASICs) have been proposed as transducers of sensory stimuli. ASIC subunits mRNAs are largely expressed in the central nervous systems (CNS), the peripheral nervous system including dorsal root ganglia (DRG) that innervate the bladder, and the bladder (both mucosa and detrusor), suggesting the possibility that ASICs are involved in regulation of lower urinary tract (LUT) activity. In this study, we examined effects of A-317567, a non-amiloride blocker of ASICs, on activity of LUT with or without acid irritation. METHODS C57BL/6 female mice (12-13 week-old) were anesthetized with sevoflurane during surgery including precollicular decerebration. A PE-50 tube was inserted into the bladder dome to record intravesical pressure. Cystometrogram (CMG) recordings under unanesthetized conditions were performed by continuously infusing (30 μl/min) saline alone or saline followed by dilute acetic acid (A/A, pH 3). CMG parameters were: pressure threshold for inducing micturition (PT); maximal voiding pressure (MVP), bladder compliance (BCP), bladder contraction duration (BCD), and inter-contraction interval (ICI). A-317567 was infused intravesically (100 μM) or injected i.p. (30 mg/kg), and effects of the drug were compared with those of the vehicle. All values are expressed as mean ± S.E.M. For statistical analysis, two-way repeated measures ANOVA and Wilcoxon matched-pairs signed rank test were used, and P ≤ 0.05 was considered significant. RESULTS I.p. administration of A-317567 increased PT and ICI and decreased BCP during saline infusion CMG, whereas it produced no changes in MVP and BCD (Fig. 1A). The i.p. dose ameliorated bladder hyperactivity (i.e., exhibited as decreased ICI) induced by intravesical A/A perfusion (Fig. 1B). However, intravesical infusion of the drug had no effects on activity of the LUT either with or without acid irritation. Neither intravesical infusion nor i.p. injection of the vehicle produced significant effects on both normal LUT activity and A/A-induced bladder hyperactivity. CONCLUSIONS ASICs participate in afferent excitatory transmission controlling reflex bladder activity under conditions of the LUT either with or without acid irritation. ASICs in the DRG, the CNS or both, but not in the bladder, play the essential role. © 2014FiguresReferencesRelatedDetails Volume 191Issue 4SApril 2014Page: e135-e136 Advertisement Copyright & Permissions© 2014MetricsAuthor Information Mitsuharu Yoshiyama More articles by this author Hideki Kobayashi More articles by this author Isao Araki More articles by this author Masayuki Takeda More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Effects of urethane on reflex activity of lower urinary tract in decerebrate unanesthetized rats

Effects of urethane on lower urinary tract function were examined in decerebrate unanesthetized rats. During single slow infusion (0.04 ml/min) cystometrograms (CMGs), urethane (0.3 g/kg) increased micturition pressure threshold (PT) by 73%, postvoid residual volume (RV) by 425%, and decreased voiding efficiency (VE) by 57%, but did not change maximal voiding pressure (MVP), closing peak pressure (CPP), bladder compliance, bladder contraction duration (BCD), or volume threshold (VT) for inducing micturition. Lower doses (0.01-0.1 g/kg) did not alter any parameter. During continuous fast infusion (0.21 ml/min) CMGs, urethane at doses of 0.6-1.2 g/kg (iv) markedly decreased CPP by 69-85%, whereas only the largest dose (1.2 g/kg iv) decreased MVP and external urethral sphincter electromyogram activity by 42 and by 80%, respectively. Doses of 0.001-0.6 g/kg did not alter the intercontraction interval and BCD. Taken together, these results suggest that urethral activity, which is essential for efficient voiding, is more sensitive to the suppressive effect of urethane than afferent or efferent mechanisms controlling the bladder. The threshold dose of MK-801 (0.3 mg/kg), an NMDA antagonist, required to decrease MVP and increase VT in urethane (1.2 g/kg)-anesthetized rats, only increased VT in rats treated with a subanesthetic dose of urethane (0.3 g/kg), suggesting a higher sensitivity of the afferent vs. efferent limb of the micturition reflex pathway to urethane-MK-801 interactions. Because effects of urethane persisted after removal of the forebrain, they must be mediated by actions on the brain stem, spinal cord, or peripheral nervous system.

Sex-related differences in activity of lower urinary tract in response to intravesical acid irritation in decerebrate unanesthetized mice

Sex-related differences in lower urinary tract (LUT) activity responding to intravesical infusion of diluted acetic acid (A/A, pH 3.0) were investigated during cystometrograms in decerebrate unanesthetized mice. A/A produced a decrease of intercontraction intervals in both female and male animals, and the extent of the decrease in male mice was much less than in female mice [19 +/- 5% (P = 0.03) vs. 65 +/- 5% (P = 0.03); n = 6 for each], exhibiting a marked difference between the two groups in response to acid irritation of the LUT (P = 0.002). A/A reduced maximal voiding pressure (MVP) (19 +/- 4%, P = 0.03) but had no effect on pressure threshold for inducing voiding contraction (PT) (P = 0.56) in females, whereas A/A did not change MVP (P = 1.00) but increased PT (16 +/- 4%, P = 0.03) in males. A/A decreased bladder compliances of female and male mice in a similar fashion (44 +/- 10% vs. 24 +/- 7%, P = 0.03 for each). In male mice, A/A produced persistent dribbling of fluid after voiding contraction phase, which was virtually not seen in females. The present study demonstrates the differences between female and male mice in response to noxious stimulation in the LUT: the female bladder is more sensitive to the acid irritation, while the male urethra is more irritable to the noxious stimulus. Identification of mechanisms underlying sex-specific characteristics might be helpful for elucidating pathogenesis of painful bladder syndrome.

195: Effects of a Combined 5HT3 Receptor Antagonist and Noradrenaline Reuptake Inhibitor on Lower Urinary Tract Activity

You have accessJournal of UrologyDiscussed Poster, Sunday, May 21, 2006, 9:00 am - 12:00 pm1 Apr 2006195: Effects of a Combined 5HT3 Receptor Antagonist and Noradrenaline Reuptake Inhibitor on Lower Urinary Tract Activity Matthew O. Fraser, China Chien, Mary A. Katofiasc, Christopher L. Langdale, Jacqueline D. Brooks, Melissa C. Young, Kenneth J. Olejar, Venkateswarlu Karicheti, and Karl B. Thor Matthew O. FraserMatthew O. Fraser More articles by this author , China ChienChina Chien More articles by this author , Mary A. KatofiascMary A. Katofiasc More articles by this author , Christopher L. LangdaleChristopher L. Langdale More articles by this author , Jacqueline D. BrooksJacqueline D. Brooks More articles by this author , Melissa C. YoungMelissa C. Young More articles by this author , Kenneth J. OlejarKenneth J. Olejar More articles by this author , Venkateswarlu KarichetiVenkateswarlu Karicheti More articles by this author , and Karl B. ThorKarl B. Thor More articles by this author View All Author Informationhttps://doi.org/10.1016/S0022-5347(18)32462-5AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail "195: Effects of a Combined 5HT3 Receptor Antagonist and Noradrenaline Reuptake Inhibitor on Lower Urinary Tract Activity." The Journal of Urology, 175(4S), pp. 63–64 © 2016 by American Urological AssociationFiguresReferencesRelatedDetails Volume 175Issue 4SApril 2006Page: 63-64 Advertisement Copyright & Permissions© 2016 by American Urological AssociationMetricsAuthor Information Matthew O. Fraser More articles by this author China Chien More articles by this author Mary A. Katofiasc More articles by this author Christopher L. Langdale More articles by this author Jacqueline D. Brooks More articles by this author Melissa C. Young More articles by this author Kenneth J. Olejar More articles by this author Venkateswarlu Karicheti More articles by this author Karl B. Thor More articles by this author Expand All Advertisement Loading ...

Effects of tiropramide on the activity of lower urinary tract in dogs and its interpretation

The rhythmic contractions of urinary bladder under constant volume condition were evoked in decerebrate and de-anesthetized dogs, while various myogenic and nerve-mediated electrical and mechanical activities of smooth muscles were recorded from in vivo pelvic viscera. The vesical rhythmic contractions were transiently and partially blocked by intravenous application of tiropromide. This 'partial' block showed a good contrast to the 'complete' block of identical contractions, which was observed after application of oxybutynin, known as a potent anti-muscarinic drug. The bladder voiding cycles were observed in other decerebrate dogs, while the warmed Ringer solution was infused at a steady rate into the dome of the bladder until principal voiding contraction occurred in cystometric recordings. The initiation of voiding contraction was markedly delayed after intravenous injection of tiropramide. The delay of principal contraction was found to be due to successive appearance of falling waves in cystometric recordings. As a evident contrast, terodiline caused a significant reduction of voiding contraction height and shortening of clonic discharge phase of external urethral sphincters during voiding cycle. It is concluded that tiropramide does not reveal anti-muscarinic action which oxybutynin or terodiline does really show, instead tiropramide acts principally on bladder detrusor itself, especially on its relaxation phase of premature contraction to be prolonged. The evidences were also presented for electrophysiological identification of bladder detrusor and urethral smooth muscle.