Role of vasopressin V1A receptor in the urethral closure reflex in rats

2011 ◽  
Vol 300 (4) ◽  
pp. F976-F982 ◽  
Author(s):  
Hiroyuki Ueno ◽  
Masako Kuno ◽  
Yasushi Shintani ◽  
Izumi Kamo
Keyword(s):  
Spinal Cord ◽  
Pressure Rise ◽  
Physiological Role ◽  
Female Rats ◽  
Reflex Response ◽  
Abdominal Pressure ◽  
Intravesical Pressure ◽  
Urethral Closure ◽  
Urethral Resistance ◽  
Vasopressin V1a Receptor

An enhanced urethral closure reflex via the spinal cord is related to urethral resistance elevation during increased abdominal pressure. However, with the exception of monoamines, neurotransmitters modulating this reflex are not understood. We investigated whether the vasopressin V1A receptor (V1AR) is involved in the urethral closure reflex in urethane-anesthetized female rats. V1AR mRNA was highly expressed among the vasopressin receptor family in the total RNA purified from lamina IX in the spinal cord L6–S1 segment. In situ hybridization analysis of the spinal L6–S1 segment confirmed that these positive signals from the V1ARs were only detected in lamina IX. Intrathecally injected Arg8-vasopressin (AVP), an endogenous ligand, significantly increased urethral resistance during an intravesical pressure rise, and its effect was blocked by the V1AR antagonist. AVP did not increase urethral resistance in rats in which the pelvic nerves were transected bilaterally. Urethral closure reflex responses to the intravesical pressure rise increased by up to threefold compared with the baseline response after AVP administration in contrast to no increase by vehicle. In addition, intravenously and intrathecally injected V1AR antagonists decreased urethral resistance. These results suggest that V1AR stimulation in the spinal cord enhances the urethral closure reflex response, thereby increasing urethral resistance during an abdominal pressure rise and that V1AR plays a physiological role in preventing urine leakage.

Urethral closure mechanisms under sneeze-induced stress condition in rats: a new animal model for evaluation of stress urinary incontinence

2003 ◽  
Vol 285 (2) ◽  
pp. R356-R365 ◽  
Author(s):  
Izumi Kamo ◽  
Kazumasa Torimoto ◽  
Michael B. Chancellor ◽  
William C. de Groat ◽  
Naoki Yoshimura
Keyword(s):  
Urinary Incontinence ◽  
Stress Condition ◽  
Female Rats ◽  
Urinary Continence ◽  
Abdominal Pressure ◽  
Intravesical Pressure ◽  
External Urethral Sphincter ◽  
Urinary Leakage ◽  
Induced Stress ◽  
Urethral Closure

The urethral closure mechanism under a stress condition induced by sneezing was investigated in urethane-anesthetized female rats. During sneezing, while the responses measured by microtip transducer catheters in the proximal and middle parts of the urethra increased, the response in the proximal urethra was almost negligible when the bladder response was subtracted from the urethral response or when the abdomen was opened. In contrast, the response in the middle urethra during sneezing was still observed after subtracting the bladder response or after opening the abdomen. These responses in the middle urethra during sneezing were significantly reduced ∼80% by bilateral transection of the pudendal nerves and the nerves to the iliococcygeous and pubococcygeous muscles but not by transection of the visceral branches of the pelvic nerves and hypogastric nerves. The sneeze leak point pressure was also measured to investigate the role of active urethral closure mechanisms in maintaining total urethral resistance against sneeze-induced urinary incontinence. In sham-operated rats, no urinary leakage was observed during sneeze, which produced an increase of intravesical pressure up to 37 ± 2.2 cmH2O. However, in nerve-transected rats urinary leakage was observed when the intravesical pressure during sneezing exceeded 16.3 ± 2.1 cmH2O. These results indicate that during sneezing, pressure increases elicited by reflex contractions of external urethral sphincter and pelvic floor muscles occur in the middle portion of the urethra. These reflexes in addition to passive transmission of increased abdominal pressure significantly contribute to urinary continence mechanisms under a sneeze-induced stress condition.

Involvement of reflex urethral closure mechanisms in urethral resistance under momentary stress condition induced by electrical stimulation of rat abdomen

2007 ◽  
Vol 293 (3) ◽  
pp. F920-F926 ◽  
Author(s):  
Izumi Kamo ◽  
Tadatoshi Hashimoto
Keyword(s):  
Urinary Incontinence ◽  
Electrical Stimulation ◽  
Abdominal Pressure ◽  
Intravesical Pressure ◽  
Leak Point Pressure ◽  
Pelvic Nerves ◽  
Urethral Closure ◽  
Urethral Resistance ◽  
Point Pressure ◽  
Stimulation Of

A novel method for evaluating the urethral resistance during abrupt elevation of abdominal pressure was developed in spinalized female rats under urethane anesthesia. Electrical stimulation of abdominal muscles for 1 s induced increases in both the intra-abdominal and the intravesical pressure in a stimulus-dependent manner, and the bladder response was almost lost when the abdomen was opened. The lowest intravesical pressure during electrical stimulation that induced fluid leakage from the urethral orifice (leak point pressure) and the maximal intravesical pressure without urine leakage below the leak point pressure were evaluated as the indexes of urethral resistance. Lower urethral resistance was obtained in the rats whose pelvic nerves or somatic nerves containing pudendal nerves and nerves to iliococcygeus/pubococcygeus muscles were transected bilaterally. In contrast, transection of bilateral hypogastric nerves showed smaller effects. Duloxetine, a drug for stress urinary incontinence, enlarged the reflex urethral closing contractions that were induced by an increase in intravesical pressure and measured using a microtip transducer catheter in the middle urethra. This drug also increased the urethral resistance (leak point pressure), whereas it did not show any effect in the rats whose pelvic nerves were bilaterally transected, showing that the augmentation of the reflex urethral closure by the drug resulted in the elevation of the urethral resistance. From these findings, it was concluded that during momentary elevation of abdominal pressure, the reflex urethral closure mechanisms via bladder-spinal cord-urethral sphincter and pelvic floor muscles greatly contribute to the increase in the urethral resistance to prevent the urinary incontinence.

The role of bladder-to-urethral reflexes in urinary continence mechanisms in rats

2004 ◽  
Vol 287 (3) ◽  
pp. F434-F441 ◽  
Author(s):  
Izumi Kamo ◽  
Tracy W. Cannon ◽  
Deirdre A. Conway ◽  
Kazumasa Torimoto ◽  
Michael B. Chancellor ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Female Rats ◽  
Reflex Response ◽  
Bladder Pressure ◽  
Urinary Continence ◽  
Nerve Transection ◽  
Pelvic Nerve ◽  
Urethral Orifice ◽  
Intact Rats ◽  
Urethral Reflexes

Urethral closure mechanisms during passive increments in intravesicular pressure (Pves) were investigated using microtip transducer catheters in urethane-anesthetized female rats. After a block of reflex bladder contractions by spinal cord transection at T8-T9, abruptly raising Pves to 20, 40, or 60 cmH2O for 2 min induced a bladder pressure-dependent contractile response in a restricted portion of the middle urethra (12.5–15 mm from the urethral orifice) that was abolished by cutting the pelvic nerves bilaterally. In pelvic nerve-intact rats, the bilateral transection of either the pudendal nerves, the nerves to the iliococcygeous/pubococcygeous muscles, or the hypogastric nerves significantly reduced (49–74%) the urethral reflex response induced by passive Pves increases, and combined transection of these three sets of nerves totally abolished the urethra-closing responses. In spinal cord-intact rats, similar urethral contractile responses were elicited during Pves elevation (20 or 40 cmH2O) and were also eliminated by bilateral pelvic nerve transection. After spinal cord and pelvic nerve transection, leak point pressures, defined as the pressure inducing fluid leakage from the urethral orifice during passive Pves elevation by either bladder pressure clamping in 2.5-cmH2O steps or direct compression of the bladder, were significantly lowered by 30–35% compared with sham-operated (spinal cord-transected and pelvic nerve-intact) rats. These results indicate that 1) passive elevation of Pves can elicit pelvic afferent nerve-mediated contractile reflexes in the restricted portion of the urethra mediated by activation of sympathetic and somatic nerves and 2) bladder-to-urethral reflexes induced by passive Pves elevation significantly contribute to the prevention of stress urinary incontinence.

scholarly journals Increased duration of simulated childbirth injuries results in increased time to recovery

2007 ◽  
Vol 292 (4) ◽  
pp. R1738-R1744 ◽  
Author(s):  
H. Q. Pan ◽  
J. M. Kerns ◽  
D. L. Lin ◽  
S. Liu ◽  
N. Esparza ◽  
...  
Keyword(s):  
Virgin Female ◽  
Female Rats ◽  
Abdominal Pressure ◽  
Leak Point Pressure ◽  
Second Stage Of Labor ◽  
Inflated Balloon ◽  
Pressure Testing ◽  
Acute Injuries ◽  
Urethral Resistance ◽  
Point Pressure

Stress urinary incontinence (SUI) development is strongly correlated with vaginal childbirth, particularly increased duration of the second stage of labor. However, the mechanisms of pelvic floor injury leading to SUI are largely unknown. The aim of this study was to determine the effects of increased duration of vaginal distension (VD) on voiding cystometry, leak point pressure testing, and histology. Sixty-nine virgin female rats underwent VD with an inflated balloon for either 1 or 4 h, while 33 age-matched rats were sham-VD controls. Conscious cystometry, leak point pressure testing, and histopathology were determined 4 days, 10 days, and 6 wk after VD. The increase in abdominal pressure to leakage (LPP) during leak point pressure testing was significantly decreased in both distension groups 4 days after distension, indicative of short-term decreased urethral resistance. Ten days after VD, LPP was significantly decreased in the 4-h but not the 1-h distension group, indicating that a longer recovery time is needed after longer distension duration. Six weeks after VD, LPP was not significantly different from sham-VD values, indicating a return toward normal urethral resistance. In contrast, 6 wk after VD of either duration, the distended rats had not undergone the same increase in voided volume as the sham-VD group, suggesting that some effects of VD do not resolve within 6 wk. Both VD groups demonstrated histopathological evidence of acute injuries and tissue remodeling. In conclusion, this experiment suggests pressure-induced hypoxia as a possible mechanism of injury in vaginal delivery.

Alterations in the number of motoneurons containing immunoreactive calcitonin gene-related peptide(CGRP)& choline acetyltransferase(ChAT) in the cervical spinal cord of the wobbler mouse during the development of the motoneuron disease

1995 ◽  
Vol 53 ◽  
pp. 970-971
Author(s):  
L. Vacca-Galloway ◽  
Y.Q. Zhang ◽  
P. Bose ◽  
S.H. Zhang
Keyword(s):  
Spinal Cord ◽  
Early Stage ◽  
Cervical Spinal Cord ◽  
Wild Type Mouse ◽  
Reflex Response ◽  
Mouse Strains ◽  
Behavioral Tests ◽  
Wobbler Mouse ◽  
Stage 4 ◽  
Stage 1

The Wobbler mouse (wr) has been studied as a model for inherited human motoneuron diseases (MNDs). Using behavioral tests for forelimb power, walking, climbing, and the “clasp-like reflex” response, the progress of the MND can be categorized into early (Stage 1, age 21 days) and late (Stage 4, age 3 months) stages. Age-and sex-matched normal phenotype littermates (NFR/wr) were used as controls (Stage 0), as well as mice from two related wild-type mouse strains: NFR/N and a C57BI/6N. Using behavioral tests, we also detected pre-symptomatic Wobblers at postnatal ages 7 and 14 days. The mice were anesthetized and perfusion-fixed for immunocytochemical (ICC) of CGRP and ChAT in the spinal cord (C3 to C5).Using computerized morphomety (Vidas, Zeiss), the numbers of IR-CGRP labelled motoneurons were significantly lower in 14 day old Wobbler specimens compared with the controls (Fig. 1). The same trend was observed at 21 days (Stage 1) and 3 months (Stage 4). The IR-CGRP-containing motoneurons in the Wobbler specimens declined progressively with age.

Tempo-spatial integration of nociceptive stimuli assessed via the nociceptive withdrawal reflex in healthy humans.

2021 ◽  
Author(s):  
Mauricio Carlos Henrich ◽  
Ken Steffen Frahm ◽  
Ole K. Andersen
Keyword(s):  
Spinal Cord ◽  
Pain Intensity ◽  
Spatial Information ◽  
Reflex Response ◽  
Spatial Integration ◽  
Opposite Pattern ◽  
Simultaneous Stimulation ◽  
Nociceptive Withdrawal Reflex ◽  
Withdrawal Reflex ◽  
Healthy Humans

Spatial information of nociceptive stimuli applied in the skin of healthy humans is integrated in the spinal cord to determine the appropriate withdrawal reflex response. Double-simultaneous stimulus applied in different skin sites are integrated, eliciting a larger reflex response. The temporal characteristics of the stimuli also modulate the reflex e.g. by temporal summation. The primary aim of this study was to investigate how the combined tempo-spatial aspects of two stimuli are integrated in the nociceptive system. This was investigated by delivering single and double simultaneous stimulation, and sequential stimulation with different inter-stimulus intervals (ISIs ranging 30-500 ms.) to the sole of the foot of fifteen healthy subjects. The primary outcome measure was the size of the nociceptive withdrawal reflex (NWR) recorded from the Tibialis Anterior (TA) and Biceps Femoris (BF) muscles. Pain intensity was measured using an NRS scale. Results showed spatial summation in both TA and BF when delivering simultaneous stimulation. Simultaneous stimulation provoked larger reflexes than sequential stimulation in TA, but not in BF. Larger ISIs elicited significantly larger reflexes in TA, while the opposite pattern occurred in BF. This differential modulation between proximal and distal muscles suggests the presence of spinal circuits eliciting a functional reflex response based on the specific tempo-spatial characteristics of a noxious stimulus. No modulation was observed in pain intensity ratings across ISIs. Absence of modulation in the pain intensity ratings argues for an integrative mechanism located within the spinal cord governed by a need for efficient withdrawal from a potentially harmful stimulus.

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