scholarly journals Effect of duloxetine, a norepinephrine and serotonin reuptake inhibitor, on sneeze-induced urethral continence reflex in rats

2008 ◽  
Vol 295 (1) ◽  
pp. F264-F271 ◽  
Author(s):  
Minoru Miyazato ◽  
Yasuhiro Kaiho ◽  
Izumi Kamo ◽  
Michael B. Chancellor ◽  
Kimio Sugaya ◽  
...  
Keyword(s):  
Reuptake Inhibitor ◽  
Control Level ◽  
Female Rats ◽  
Urethral Pressure ◽  
Adrenoceptor Antagonist ◽  
Closure Mechanism ◽  
Urethral Orifice ◽  
Point Pressure ◽  
Vaginal Distension

We investigated the effect of duloxetine, a norepinephrine (NE) and serotonin (5-HT) reuptake inhibitor, on the neurally evoked urethral continence reflex induced by sneezing in rats. To clarify the role of noradrenergic and serotonergic mechanisms in preventing stress urinary incontinence (SUI) during sneezing, we examined the effect of duloxetine followed by intrathecal (it) methiothepin maleate (5-HT receptor and α1-adrenoceptor antagonist) or terazosin or idazoxan (selective α1- and α2-adrenoceptor antagonists, respectively). Amplitude of urethral pressure responses during sneezing (A-URS), urethral baseline pressure (UBP) at the midurethra, and sneeze-induced leak point pressure (S-LPP) were measured in normal adult female rats and rats with SUI induced by vaginal distension (VD). In normal and VD rats, intravenous application of duloxetine (1 mg/kg) increased A-URS by 35% and 34% and UBP by 21% and 34%, respectively. Sneezing-induced fluid leakage from the urethral orifice was observed in VD rats but not in normal rats. S-LPP was increased from 39.1 to 92.2 cmH2O by intravenous duloxetine in incontinent VD rats. Duloxetine-mediated enhancement of A-URS was inhibited by terazosin but not methiothepin maleate (it). In addition, simultaneous intrathecal application of methiothepin and terazosin induced a reduction in A-URS during sneezing, which was not increased by intravenous duloxetine. However, the reduced A-URS after intrathecal application of methiothepin and terazosin returned to the control level when duloxetine (iv) was applied after intrathecal idazoxan administration. These results indicate that duloxetine can prevent SUI by facilitating noradrenergic and serotonergic systems in the spinal cord to enhance the sneeze-induced active urethral closure mechanism.

Role of noradrenergic pathways in sneeze-induced urethral continence reflex in rats

2007 ◽  
Vol 292 (2) ◽  
pp. F639-F646 ◽  
Author(s):  
Yasuhiro Kaiho ◽  
Izumi Kamo ◽  
Michael B. Chancellor ◽  
Yoichi Arai ◽  
William C. de Groat ◽  
...  
Keyword(s):  
Reuptake Inhibitor ◽  
Normal Female ◽  
Urethral Pressure ◽  
Adult Rats ◽  
Urethral Orifice ◽  
Norepinephrine Reuptake Inhibitor ◽  
Point Pressure ◽  
Selective Blocker ◽  
Norepinephrine Reuptake

To clarify the role of noradrenergic pathways in preventing stress urinary incontinence (SUI) during sneezing, we investigated the effect of the norepinephrine reuptake inhibitor nisoxetine and α-adrenoceptor antagonists phentolamine (nonspecific blocker) and prazosin (α1-receptor-selective blocker) on the neurally evoked urethral continence reflex induced by sneezing in rats. The amplitude of urethral pressure responses during sneezing (A-URS), urethral baseline pressure (UBP) at the midurethra, and sneeze-induced leak point pressure (S-LPP) were measured in normal female adult rats and rats with SUI induced by vaginal distention (VD). In normal rats, intrathecal (it) phentolamine (0.02 nmol) and prazosin (0.02 nmol) decreased A-URS by 11.9 and 15.7%, respectively, without affecting UBP. In both normal and VD rats, intravenous (iv) application of nisoxetine (1 mg/kg) increased A-URS by 17.2 and 18.3% and UBP by 23.7 and 32.7%, respectively. Phentolamine or prazosin (both it) eliminated nisoxetine-induced increases in A-URS, but not the increases in UBP, which were, however, suppressed by iv phentolamine (5 mg/kg) or prazosin (1 mg/kg). Sneezing induced fluid leakage from the urethral orifice in VD rats, but not in normal rats. In VD rats, S-LPP was increased by 30.2% by iv nisoxetine. Application of phentolamine and prazosin (both it) decreased S-LPP by 15.7 and 20.6%, respectively, and nisoxetine induced increases in S-LPP to 13.2 and 12.3%, respectively. These results indicate that activation of the noradrenergic system by a norepinephrine reuptake inhibitor can prevent SUI via α1-adrenoceptors by enhancing the sneeze-induced active urethral closure mechanism at the spinal level and augmenting UBP at the periphery.

scholarly journals Role of the serotonergic system in urethral continence reflexes during sneezing in rats

2018 ◽  
Vol 315 (1) ◽  
pp. F79-F85 ◽  
Author(s):  
Takahisa Suzuki ◽  
Takahiro Shimizu ◽  
Joonbeom Kwon ◽  
Eiichiro Takaoka ◽  
Satoru Yoshikawa ◽  
...  
Keyword(s):  
Female Rats ◽  
Normal Female ◽  
Urethral Pressure ◽  
Leak Point Pressure ◽  
Synthesis Inhibitor ◽  
Female Adult ◽  
Adult Rats ◽  
Urethral Closure ◽  
Point Pressure

To clarify the role of serotonin (5-HT) in the prevention of stress urinary incontinence (SUI) during sneezing, we investigated the effect of intraperitoneal application of p-chlorophenylalanine (PCPA; a serotonin synthesis inhibitor) and intravenous application of CP-809101 (a 5-HT2C agonist) or LP44 (a 5-HT7 agonist) using female rats, in which the neurally evoked continence reflex during sneezing was examined. Amplitudes of urethral pressure response during sneezing (A-URS), urethral baseline pressure (UBP) at the middle urethra, and sneeze-induced leak point pressure (S-LPP) were measured in normal female adult rats with or without drug administration. PCPA decreased A-URS by 35.1 cmH2O and UBP by 13.3 cmH2O compared with normal rats. In PCPA-administrated rats, CP-809101 increased A-URS by 24.1 cmH2O and UBP by 15.1 cmH2O, and LP44 also increased A-URS by 20.6 cmH2O and UBP by 11.4 cmH2O compared with rats treated with PCPA alone. SUI was observed with S-LPP of 40.1 cmH2O in PCPA-administrated rats, in which CP-809101 and LP44 increased S-LPP by 28.0 and 15.2 cmH2O, respectively, compared with rats treated with PCPA alone. The effects of CP-809101 and LP44 were antagonized by SB-242084 (a selective 5-HT2C antagonist) and SB-269970 (a selective 5-HT7 antagonist), respectively. These results indicate that activation of 5-HT receptors enhances the active urethral closure reflex during sneezing, at least in part via 5-HT2C and 5-HT7 receptors.

scholarly journals Circulating Secretin Activates Supraoptic Nucleus Oxytocin and Vasopressin Neurons via Noradrenergic Pathways in the Rat

Endocrinology ◽  
2010 ◽  
Vol 151 (6) ◽  
pp. 2681-2688 ◽  
Author(s):  
Sathya Velmurugan ◽  
Paula J. Brunton ◽  
Gareth Leng ◽  
John A. Russell
Keyword(s):  
Amino Acid ◽  
Firing Rate ◽  
Noradrenaline Release ◽  
Supraoptic Nucleus ◽  
Female Rats ◽  
Adrenoceptor Antagonist ◽  
Intracerebroventricular Infusion ◽  
Neuroendocrine Neurons ◽  
Vasopressin Neurons

Secretin is a 27-amino acid brain-gut peptide from duodenal S-cells. We tested the effects of systemic administration of secretin to simulate its postprandial release on neuroendocrine neurons of the supraoptic nucleus (SON) in urethane-anesthetized female rats. Secretin dose-dependently increased the firing rate of oxytocin neurons, more potently than cholecystokinin, and dose-dependently increased plasma oxytocin concentration. The effect of secretin on SON vasopressin neurons was also predominantly excitatory, in contrast to the inhibitory actions of cholecystokinin. To explore the involvement of noradrenergic inputs in secretin-induced excitation, benoxathian, an α1-adrenoceptor antagonist, was infused intracerebroventricularly. Benoxathian intracerebroventricular infusion blocked the excitation by secretin of both oxytocin and vasopressin neurons. To test the role of local noradrenaline release in the SON, benoxathian was microdialyzed onto the SON. The basal firing rate of oxytocin neurons was slightly reduced and the secretin-induced excitation was attenuated during benoxathian microdialysis. Hence, noradrenergic pathways mediate the excitation by systemic secretin of oxytocin neurons via α1-adrenoceptors in the SON. As both systemic secretin and oxytocin are involved in regulating gastrointestinal functions and natriuresis, systemically released secretin might act partly through oxytocin.

scholarly journals Rat Mesenchymal Stem Cell Secretome Promotes Elastogenesis and Facilitates Recovery from Simulated Childbirth Injury

2014 ◽  
Vol 23 (11) ◽  
pp. 1395-1406 ◽  
Author(s):  
Charuspong Dissaranan ◽  
Michelle A. Cruz ◽  
Matthew J. Kiedrowski ◽  
Brian M. Balog ◽  
Bradley C. Gill ◽  
...  
Keyword(s):  
Female Rats ◽  
Urethral Sphincter ◽  
Leak Point Pressure ◽  
External Urethral Sphincter ◽  
Paracrine Factors ◽  
Pelvic Organs ◽  
Point Pressure ◽  
Urethral Smooth Muscle ◽  
And Function ◽  
Vaginal Distension

Vaginal delivery is a risk factor for stress urinary incontinence (SUI). Mesenchymal stem cells (MSCs) home to injured organs and can facilitate repair. The goal of this study was to determine if MSCs home to pelvic organs after simulated childbirth injury and facilitate recovery from SUI via paracrine factors. Three experiments were performed. Eighteen female rats received vaginal distension (VD) or sham VD and labeled intravenous (IV) MSCs to investigate if MSCs home to the pelvic organs. Whole-organ imaging and immunofluorescence were performed 1 week later. Thirty-four female rats received VD and IV MSCs, VD and IV saline, or sham VD and IV saline to investigate if MSCs accelerate recovery of continence. Twenty-nine female rats received VD and periurethral concentrated conditioned media (CCM), VD and periurethral control media, or sham VD and periurethral control media to investigate if factors secreted by MSCs accelerate recovery from VD. Urethral histology and function were assessed 1 week later. Significantly more MSCs were observed in the urethra, vagina, and spleen after VD compared to sham VD. Continence as measured by leak point pressure (LPP) was significantly reduced after VD in rats treated with saline or control media compared to sham VD but not in those given MSCs or CCM. External urethral sphincter (EUS) function as measured by electromyography (EMG) was not improved with MSCs or CCM. Rats treated with MSCs or CCM demonstrated an increase in elastin fibers near the EUS and urethral smooth muscle more similar to that of sham-injured animals than rats treated with saline or control media. MSCs homed to the urethra and vagina and facilitated recovery of continence most likely via secretion of paracrine factors. Both MSCs and CCM have promise as novel noninvasive therapies for SUI.

scholarly journals Diabetes slows the recovery from urinary incontinence due to simulated childbirth in female rats

2007 ◽  
Vol 293 (2) ◽  
pp. R950-R955 ◽  
Author(s):  
Ja-Hong Kim ◽  
Xiao Huang ◽  
Guiming Liu ◽  
Courtenay Moore ◽  
James Bena ◽  
...  
Keyword(s):  
Urinary Incontinence ◽  
External Sphincter ◽  
Bladder Capacity ◽  
Diabetic Rats ◽  
Female Rats ◽  
Sprague Dawley ◽  
Leak Point Pressure ◽  
Sprague Dawley Rats ◽  
Point Pressure ◽  
Vaginal Distension

This study was done to test the hypothesis that simulated vaginal birth by vaginal distension (VD) causes more severe urinary incontinence and slower recovery in diabetic rats. After measuring baseline leak point pressure (LPP) in 16 diabetes mellitus (DM) and 16 age- and weight-matched control (Ct) female Sprague-Dawley rats, these animals underwent either VD or sham VD (sham). Four and ten days after the procedures, LPP and conscious cystometry were assessed. Tissues were then harvested and examined by light microscopy. LPP at baseline was equal among all four groups. Four days after VD, LPP in both VD groups dropped to significantly lower levels than in sham rats ( P < 0.001). Moreover, LPP in the DM+VD group was significantly lower than in the Ct+VD group. At 10 days, LPP in the Ct+VD group had recovered to its baseline value, whereas the LPP in the DM+VD group remained significantly reduced. DM rats had larger bladder capacity and longer voiding intervals than Ct rats. Histological findings included more severe damage to the external sphincter striated musculature of the urethra in DM+VD group compared with Ct+VD. In conclusion, these findings suggest that DM causes increased severity and delayed functional recovery from the effects of simulated childbirth.

scholarly journals Role of spinal serotonergic pathways in sneeze-induced urethral continence reflex in rats

2009 ◽  
Vol 297 (4) ◽  
pp. F1024-F1031 ◽  
Author(s):  
Minoru Miyazato ◽  
Yasuhiro Kaiho ◽  
Izumi Kamo ◽  
Takeya Kitta ◽  
Michael B. Chancellor ◽  
...  
Keyword(s):  
Receptor Subtypes ◽  
Normal Female ◽  
Urethral Pressure ◽  
Female Adult ◽  
Adult Rats ◽  
Way 100635 ◽  
Urethral Closure ◽  
Point Pressure ◽  
It Application

To clarify the role of spinal serotonergic mechanisms in preventing stress urinary incontinence (SUI) during sneezing, we investigated the effect of intrathecal (it) application of 8-OH-DPAT (a 5-HT1A agonist), mCPP (a 5-HT2B/2C agonist), and fluoxetine (a serotonin reuptake inhibitor) using a rat model that can examine the neurally evoked continence reflex during sneezing. Amplitudes of urethral pressure responses during sneezing (A-URS), urethral baseline pressure (UBP) at the midurethra, and sneeze-induced leak point pressure (S-LPP) were measured in normal female adult rats and rats with SUI induced by vaginal distention (VD). In normal rats, 8-OH-DPAT decreased A-URS by 48.9%, whereas mCPP increased A-URS by 33.6%. However, A-URS was not changed after fluoxetine. 8-OH-DPAT, mCPP, or fluoxetine did not alter UBP. The effect of 8-OH-DPAT and mCPP was antagonized by WAY-100635 (it), a selective 5-HT1A antagonist, and RS-102221 (it), a selective 5-HT2C antagonist, respectively. Fluoxetine in the presence of WAY-100635 did not change either A-URS or UBP, but fluoxetine in the presence of RS-102221 decreased A-URS. In VD rats, S-LPP was decreased by 14.6 cmH2O after 8-OH-DPAT, whereas it was increased by 12.8 cmH2O after mCPP. However, S-LPP was not changed after fluoxetine. These results indicate that activation of 5-HT2C receptors enhances the active urethral closure reflex during sneezing at the spinal level, whereas 5-HT1A inhibits it and that no apparent changes in the sneeze-induced continence reflex after fluoxetine treatment are due to coactivation of excitatory 5-HT2C receptors and inhibitory 5-HT receptors other than the 5-HT1A subtype. Thus, activation of excitatory 5-HT receptor subtypes such as 5-HT2C could be effective for the treatment of SUI.

SOME ASPECTS OF THE FUNCTION OF FSH- AND LH-LIKE HORMONES IN NORMAL AND HYPOPHYSECTOMIZED FEMALE RATS, IN CONNECTION WITH RESERPINE ADMINISTRATION

1965 ◽  
Vol 49 (1) ◽  
pp. 28-38
Author(s):  
M. Grönroos ◽  
E. Mäkinen ◽  
K. Lahtinen ◽  
R. Tirri
Keyword(s):  
Mechanism Of Action ◽  
Biological Effect ◽  
Female Rats ◽  
Histological Picture ◽  
Peripheral Effect ◽  
Pituitary Secretion

ABSTRACT The effect of reserpine on the secretion of FSH and LH was studied as well as the role of the peripheral effect of reserpine after hypophysectomy. The results in the unoperated animals suggest that reserpine inhibits the pituitary secretion of both FSH and LH. Both these hormones combined with reserpine had a very different biological effect than was seen without reserpine. HCG (LH-like) and particularly PMS (FSH-like) hormones combined with reserpine caused definite enlargement of the ovaries. In the hypophysectomized groups, the effect of the PMS and HCG hormones administered together with reserpine or without it was the same with regard to the weight of the ovaries, but not with regard to their histological picture. On the basis of these results, reserpine may be said to have a peripheral effect although the nature of its mechanism of action is difficult to state. Reserpine probably affects the ovaries by inhibiting the follicular cycle and, consequently, the formation of new and more mature follicles.

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