Inhibitory and excitatory perigenital-to-bladder spinal reflexes in the cat

This study revealed that in awake chronic spinal cord-injured (SCI) cats reflexes from perigenital skin area to the bladder can be either inhibitory or excitatory. Electrical perigenital stimulation at frequencies between 5 and 7 Hz significantly inhibited large-amplitude rhythmic reflex bladder activity, whereas frequencies between 20 and 40 Hz induced large-amplitude bladder contractions even at low bladder volumes when reflex bladder activity was absent. Both inhibitory and excitatory effects were enhanced as the stimulation intensity increased (5–30 V, 0.2-ms pulse width). During cystometrograms, the inhibitory stimulation (7 Hz) significantly increased the micturition volume threshold 35 ± 13% above the control volume, while the excitatory stimulation (30 Hz) significantly reduced the threshold 21 ± 3%. Mechanical perigenital stimulation applied by repeated light stroking of the perigenital skin with a cotton swab only induced an excitatory effect on the bladder. Both electrical and mechanical perigenital stimuli induced large-amplitude (>30 cmH2O) bladder contractions that were relatively consistent over a range of bladder volumes (10–90% of the capacity). However, the excitatory electrical stimulation only induced bladder contractions lasting on average 42.2 ± 3.9 s, but the mechanical stimulation induced bladder contractions that lasted as long as the stimulation continued (2–3 min). Excitatory electrical or mechanical perigenital stimulation also induced poststimulus voiding. The ability to either inhibit or excite the bladder by noninvasive methods could significantly transform the current clinical management of bladder function after SCI.

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Effects of capsaicin on micturition and associated reflexes in rats

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1993.265.1.r132 ◽

1993 ◽

Vol 265 (1) ◽

pp. R132-R138 ◽

Cited By ~ 9

Author(s):

C. L. Cheng ◽

C. P. Ma ◽

W. C. de Groat

Keyword(s):

Urinary Bladder ◽

Large Dose ◽

Urethral Catheter ◽

Female Rats ◽

Bladder Function ◽

Intravesical Pressure ◽

Pressor Responses ◽

Bladder Activity ◽

Micturition Volume ◽

Stimulation Of

The effect of capsaicin on micturition and associated reflexes was studied in urethan-anesthetized female rats. Capsaicin or vehicle solution were administered 4 days before the experiment in a dose of 125 mg/kg sc or during the experiment in a dose of 50-100 mg/kg sc. Activity of the urinary bladder was recorded by measuring intravesical pressure via a urethral catheter while slowly filling (0.052 ml/min) the bladder or when the bladder was distended beyond the micturition threshold and maintained at a constant volume. Pretreatment with capsaicin did not significantly change various parameters of urinary bladder function including micturition volume threshold or the amplitude, duration, and interval between reflex bladder contractions. However, capsaicin pretreatment significantly reduced (80% decrease) the arterial pressor responses accompanying reflex bladder contractions and reduced by approximately one-half the percentage of animals in which bladder activity was inhibited by stimulation of the uterine cervix. A large dose of capsaicin (50 mg/kg sc) elicited an acute block of bladder activity that persisted for 8-15 h. This effect is attributable to an action on myelinated afferent or efferent components of the micturition reflex pathway. It is concluded that capsaicin-sensitive afferents are not essential for the performance of micturition in the rat. However, these afferents are involved in cervicovesical reflex mechanisms that modulate bladder activity and in vascular reflexes triggered by isometric bladder contractions.

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1619 EFFECTS OF INTRATHECAL INJECTION OF ALPHA-1A AND -1D ADRENOCEPTOR BLOCKERS ON BLADDER ACTIVITY IN SPINAL CORD INJURED RATS

The Journal of Urology ◽

10.1016/j.juro.2010.02.1399 ◽

2010 ◽

Vol 183 (4S) ◽

Author(s):

Katsumi Kadekawa ◽

Minoru Miyazato ◽

Saori Nishijima ◽

Katsuhiro Ashitomi ◽

Kimio Sugaya

Keyword(s):

Spinal Cord ◽

Intrathecal Injection ◽

Bladder Activity ◽

Spinal Cord Injured

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Effects of m-chlorophenylpiperazine on penile and bladder function in rats

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1989.257.6.r1441 ◽

1989 ◽

Vol 257 (6) ◽

pp. R1441-R1449 ◽

Cited By ~ 7

Author(s):

W. D. Steers ◽

W. C. de Groat

Keyword(s):

Peripheral Nerves ◽

Bladder Function ◽

Neural Firing ◽

Cavernous Nerve ◽

Cholinergic Pathways ◽

Serotonin Agonist ◽

Bladder Activity ◽

Chronic Spinal Rats ◽

Ganglionic Blocking ◽

Nerve Discharge

The effects of m-chlorophenylpiperazine (MCPP), a serotonin agonist, on spontaneous and evoked neural firing in nerves supplying the penis and bladder were examined in the urethan-anesthetized rat. MCPP (0.1-10 mg/kg iv) elicited, after a 2- to 4-min delay, an increase in spontaneous firing in cavernous nerves but no detectable firing in bladder nerves. The cavernous nerve firing was accompanied by an increase in intracavernous pressure and a depression of rhythmic bladder activity. Administration of ganglionic-blocking agents or transection of peripheral nerves revealed that the cavernous nerve discharge was mediated by activation of pre-ganglionic cholinergic pathways in the pelvic nerve. The effects of MCPP were noted in intact as well as in acute and chronic spinal rats and were prevented by the administration of the serotonin (5-HT) antagonist, metergoline (3 mg/kg im). These data indicate that pharmacological activation of 5-HT receptors, possibly of the 5-HT1B subtype, can facilitate the sacral preganglionic outflow to the penis and inhibit bladder activity.

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Effect of capsaicin on the micturition reflex in normal and chronic spinal cord-injured cats

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1999.277.3.r786 ◽

1999 ◽

Vol 277 (3) ◽

pp. R786-R794 ◽

Cited By ~ 12

Author(s):

Chen-Li Cheng ◽

Jiang-Chuan Liu ◽

Sun-Yran Chang ◽

Cheng-Ping Ma ◽

William C. de Groat

Keyword(s):

Spinal Cord ◽

Urinary Bladder ◽

Neurogenic Bladder ◽

Essential Role ◽

Bladder Dysfunction ◽

Neurogenic Bladder Dysfunction ◽

C Fiber ◽

Bladder Afferents ◽

Bladder Activity ◽

Spinal Cord Injured

The effect of capsaicin (10–80 mg/kg sc) on reflex activity of the urinary bladder was examined in anesthetized normal as well as anesthetized and awake chronic spinal cord-injured (SCI) cats. In normal cats, capsaicin elicited a transient increase in the frequency of isovolumetric bladder contractions and reduced the volume threshold for inducing micturition, but did not depress the amplitude of bladder contractions or the reflex firing on bladder nerves. In anesthetized SCI cats, capsaicin depressed reflex bladder activity and firing on bladder nerves. In awake SCI cats, capsaicin initially decreased the volume threshold for inducing micturition; however, after a delay of 3–6 h the volume threshold increased and intravesical voiding pressure decreased. This effect persisted for 4–12 days. It is concluded that capsaicin-sensitive C fiber bladder afferents are not involved in initiating reflex micturition in normal cats, but play an essential role in triggering automatic micturition in chronic SCI cats. The results are consistent with the clinical data indicating that C fiber bladder afferents contribute to bladder hyperactivity and incontinence in patients with neurogenic bladder dysfunction.

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A noninvasive ultrasonographic method to evaluate bladder function recovery in spinal cord injured rats

Experimental Neurology ◽

10.1016/j.expneurol.2005.01.027 ◽

2005 ◽

Vol 194 (1) ◽

pp. 120-127 ◽

Cited By ~ 17

Author(s):

Hans S. Keirstead ◽

Vadim Fedulov ◽

Frank Cloutier ◽

Oswald Steward ◽

Barry P. Duel

Keyword(s):

Spinal Cord ◽

Bladder Function ◽

Function Recovery ◽

Spinal Cord Injured

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V1 INTRASPINAL NERVE RE-ROUTING TO REESTABLISH BLADDER FUNCTION IN SPINAL CORD INJURED PATIENTS

European Urology Supplements ◽

10.1016/s1569-9056(07)61066-5 ◽

2007 ◽

Vol 6 (2) ◽

pp. 293 ◽

Cited By ~ 2

Author(s):

K.D. Sievert ◽

B. Winter ◽

A. Anastasiadis ◽

B. Amend ◽

A. Badke ◽

...

Keyword(s):

Spinal Cord ◽

Bladder Function ◽

Injured Patients ◽

Spinal Cord Injured

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Modulation of bladder function by luminal adenosine turnover and A1 receptor activation

AJP Renal Physiology ◽

10.1152/ajprenal.00566.2011 ◽

2012 ◽

Vol 303 (2) ◽

pp. F279-F292 ◽

Cited By ~ 8

Author(s):

H. Sandeep Prakasam ◽

Heather Herrington ◽

James R. Roppolo ◽

Edwin K. Jackson ◽

Gerard Apodaca

Keyword(s):

Receptor Activation ◽

Adenosine Kinase ◽

Nucleoside Transporters ◽

Bladder Function ◽

Extracellular Adenosine ◽

Equilibrative Nucleoside Transporters ◽

Lack Of Information ◽

Bladder Activity ◽

A1 Receptor ◽

A Site

The bladder uroepithelium transmits information to the underlying nervous and musculature systems, is under constant cyclical strain, expresses all four adenosine receptors (A1, A2A, A2B, and A3), and is a site of adenosine production. Although adenosine has a well-described protective effect in several organs, there is a lack of information about adenosine turnover in the uroepithelium or whether altering luminal adenosine concentrations impacts bladder function or overactivity. We observed that the concentration of extracellular adenosine at the mucosal surface of the uroepithelium was regulated by ecto-adenosine deaminase and by equilibrative nucleoside transporters, whereas adenosine kinase and equilibrative nucleoside transporters modulated serosal levels. We further observed that enriching endogenous adenosine by blocking its routes of metabolism or direct activation of mucosal A1 receptors with 2-chloro- N6-cyclopentyladenosine (CCPA), a selective agonist, stimulated bladder activity by lowering the threshold pressure for voiding. Finally, CCPA did not quell bladder hyperactivity in animals with acute cyclophosphamide-induced cystitis but instead exacerbated their irritated bladder phenotype. In conclusion, we find that adenosine levels at both surfaces of the uroepithelium are modulated by turnover, that blocking these pathways or stimulating A1 receptors directly at the luminal surface promotes bladder contractions, and that adenosine further stimulates voiding in animals with cyclophosphamide-induced cystitis.

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Activation of soluble guanylyl cyclase by BAY 58-2667 improves bladder function in cyclophosphamide-induced cystitis in mice

AJP Renal Physiology ◽

10.1152/ajprenal.00041.2016 ◽

2016 ◽

Vol 311 (1) ◽

pp. F85-F93 ◽

Cited By ~ 10

Author(s):

Mariana G. de Oliveira ◽

Fabiano B. Calmasini ◽

Eduardo C. Alexandre ◽

Gilberto De Nucci ◽

Fabíola Z. Mónica ◽

...

Keyword(s):

Guanylyl Cyclase ◽

Soluble Guanylyl Cyclase ◽

Bladder Capacity ◽

Bladder Function ◽

Ros Generation ◽

Promising Therapeutic Approach ◽

Protein Expressions ◽

Freely Moving ◽

Micturition Volume

Activators of soluble guanylyl cyclase (sGC) interact directly with its prosthetic heme group, enhancing the enzyme responsiveness in pathological conditions. This study aimed to evaluate the effects of the sGC activator BAY 58-2667 on voiding dysfunction, protein expressions of α1 and β1 sGC subunits and cGMP levels in the bladder tissues after cyclophosphamide (CYP) exposure. Female C57BL/6 mice (20–25 g) were injected with CYP (300 mg/kg ip) to induce cystitis. Mice were pretreated or not with BAY 58-2667 (1 mg/kg, gavage), given 1 h before CYP injection. The micturition patterns and in vitro bladder contractions were evaluated at 24 h. In freely moving mice, the CYP injection produced reduced the micturition volume and increased the number of urine spots. Cystometric recordings in CYP-injected mice revealed significant increases in basal pressure, voiding frequency, and nonvoiding contractions (NVCs), along with decreases in bladder capacity, intercontraction interval, and compliance. BAY 58-2667 significantly prevented the micturition alterations observed in both freely moving mice and cystometry and normalized the reduced in vitro carbachol-induced contractions in the CYP group. Reduced protein expressions of α1 and β1 sGC subunits and of cGMP levels were observed in the CYP group, all of which were prevented by BAY 58-2667. CYP exposure significantly increased reactive-oxygen species (ROS) generation in both detrusor and urothelium, and this was normalized by BAY 58-2667. The increased myeloperoxidase and cyclooxygenase-2 activities in the bladders of the CYP group remained unchanged by BAY 58-2667. Activators of sGC may constitute a novel and promising therapeutic approach for management of interstitial cystitis.

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