Urethral Dysfunction in Diabetic Rats

Torimoto, Kazumasa; Fraser, Matthew O.; Hirao, Yoshihiko; Groat, William C. de; Chancellor, Michael B.; Yoshimura, Naoki

doi:10.1097/01.ju.0000121283.92963.05

Cited by 87 publications

(92 citation statements)

References 16 publications

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“…Thus, decreased activity of bladder afferent pathways may cause at least in part an increase in VV in SDT rats. In addition, it was found previously that DM reduces urethral relaxation mechanisms during the voiding reflex and increases intravesical pressure thresholds for inducing urethral relaxation, thereby inducing an increase in micturition pressure in rats with streptozotocin-induced DM (22). Thus, the increase in micturition pressure observed in SDT rats could be attributable to increased urethral resistance during voiding due to DM-induced impaired urethral relaxation mechanisms.…”

Section: Resultsmentioning

confidence: 84%

Long-term effects of diabetes mellitus on voiding function in a new model of type 2 diabetes mellitus, the Spontaneously Diabetic Torii (SDT) rat

Matsumoto

Torimoto

Matsuyoshi³

et al. 2009

Biomed. Res.

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The spontaneously diabetic Torii (SDT) rat has recently been established as a model of type 2 diabetes mellitus (DM). The usefulness of this rat model for the study of diabetic voiding dysfunction was investigated. Male SDT rats and male Sprague-Dawley (SD) rats were used. Voiding function was evaluated by a metabolic cage study and cystometry. Total voided volume for 24 h, mean voided volume, and urinary frequency for 24 h were significantly greater in SDT rats at the age of 36 weeks. From cystometry mean inter-micturition interval (IMI) was significantly longer in SDT rats at the age of 22 and 36 weeks. In SDT rats mean IMI was significantly longer at the age of 36 weeks than at the age of 22 weeks. Mean voiding pressure was significantly higher in SDT rats at the age of 22 and 36 weeks. In the present study, SDT rats showed typical diabetic voiding dysfunction similar to other diabetic rat models. It was suggested that activity of the bladder afferent pathways is decreased and the urethral relaxation mechanism is impaired in SDT rats. In addition, SDT rats are suitable to study chronic diabetic voiding dysfunction because they survive without insulin treatment for as long as 60 weeks.The number of patients with diabetes mellitus (DM) is increasing all over the world. Approximately 135 million people have type 2 DM worldwide and it affects more people than type 1 DM. Therefore, it is very important to use animal models of type 2 DM to investigate the pathophysiological mechanisms and pharmacological effects from the clinical point of view. Type 2 DM is a multifactorial disease caused by hormonal imbalance between insulin secretion and peripheral insulin sensitivity (1, 2, 15). The Spontaneously Diabetic Torii (SDT) rat is an inbred rat strain established recently from a colony of normal Sprague-Dawley (SD) rats by Torii Pharmaceutical Company (19). Male SDT rats develop hyperglycemia spontaneously without obesity at 20 weeks of age, with an incident rate reaching 100% at 40 weeks of age. The SDT rat is known as a useful model of non-obese type 2 DM, and it can be a very good candidate for an animal model of type 2 DM to investigate diabetic bladder dysfunction. In this study, it was investigated whether the SDT rat is useful as an animal model of type 2 DM for the study of diabetic cystopathy. MATERIALS AND METHODSMale SDT rats were used. Male SD rats were used as controls. Animal care and handling were done in accordance with institutional guidelines and approved by the Institutional Animal Care and Use Committees at

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Section: Resultsmentioning

confidence: 84%

Long-term effects of diabetes mellitus on voiding function in a new model of type 2 diabetes mellitus, the Spontaneously Diabetic Torii (SDT) rat

Matsumoto

Torimoto

Matsuyoshi³

et al. 2009

Biomed. Res.

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“…DM neuropathy also reportedly affects urethral function in STZ-induced DM rats. DM rats exhibit a reduction in NO-mediated relaxation and an enhancement of α 1 -adrenoceptor-mediated contraction of the urethral smooth muscle during reflex bladder contractions, both possibly contributing to increased bladder outlet resistance resulting in impaired bladder emptying in DM (645,646).…”

Section: Diabetes Mellitus and Detrusor Underactivitymentioning

confidence: 99%

Neural Control of the Lower Urinary Tract

2009

Encyclopedia of Neuroscience

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This article summarizes anatomical, neurophysiological, pharmacological, and brain imaging studies in humans and animals that have provided insights into the neural circuitry and neurotransmitter mechanisms controlling the lower urinary tract. The functions of the lower urinary tract to store and periodically eliminate urine are regulated by a complex neural control system in the brain, spinal cord, and peripheral autonomic ganglia that coordinates the activity of smooth and striated muscles of the bladder and urethral outlet. The neural control of micturition is organized as a hierarchical system in which spinal storage mechanisms are in turn regulated by circuitry in the rostral brain stem that initiates reflex voiding. Input from the forebrain triggers voluntary voiding by modulating the brain stem circuitry. Many neural circuits controlling the lower urinary tract exhibit switch-like patterns of activity that turn on and off in an all-or-none manner. The major component of the micturition switching circuit is a spinobulbospinal parasympathetic reflex pathway that has essential connections in the periaqueductal gray and pontine micturition center. A computer model of this circuit that mimics the switching functions of the bladder and urethra at the onset of micturition is described. Micturition occurs involuntarily in infants and young children until the age of 3 to 5 years, after which it is regulated voluntarily. Diseases or injuries of the nervous system in adults can cause the re-emergence of involuntary micturition, leading to urinary incontinence. Neuroplasticity underlying these developmental and pathological changes in voiding function is discussed.

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“…Seven isovolumetric IVP and UPP parameters were measured: 1) the maximum amplitude of bladder contraction, 2) the duration of bladder contraction, 3) the area of reflex bladder contraction, 4) the frequency of bladder contraction, 5) the UPP baseline of the continence phase (i.e., the average UPP during bladder relaxation), 6) the UPP baseline of the voiding phase [i.e., the average UPP during the period of high-frequency oscillations (HFOs)], and 7) the difference between the two UPP baselines (i.e., the UPP baseline of the continence phase minus the UPP baseline of the voiding phase) ( Fig. 1) (2,7,45).…”

Section: General Preparations the Institutional Animal Care And Usementioning

confidence: 99%

Sexually dimorphic urethral activity in response to pharmacological activation of 5-HT_1A receptors in the rat

Fan

Chen

et al. 2013

American Journal of Physiology-Renal Physiology

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In this study, we examined the possibility that 5-HT 1A receptors may underlie sexually dimorphic mechanisms affecting the regulation of urethral functions in anesthetized rats. Simultaneous recordings of intravesical pressure under isovolumetric conditions, external urethral sphincter-electromyography, and urethral perfusion pressure were used to examine the effects of a 5-HT1A receptor agonist [8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT)] and antagonist (WAY-100635) on bladder and urethral functions. This research also evaluated the effects of 8-OH-DPAT and ␣-bungarotoxin (a neuromuscular blockade agent) on urethral continence using leak point pressure testing, and the distribution of 5-HT 1A receptors in the lower urinary tract was assessed by immunohistochemistry. The serotonergic mechanism that controls the urinary bladder and external urethral sphincter-electromyography activity showed no significant sexual differences, but urethral activity in urethral perfusion pressure and leak point pressure values exhibited some sexual differences. 8-OH-DPAT enhanced urethral pressure during continence in rats of both sexes, but the drug elevated the pressure during voiding in male rats and reduced it in female rats. The distribution of 5-HT 1A receptors in the spinal cord also showed some sexual differences. The present study contributes to our understanding of the role of 5-HT1A receptors in physiological and immunohistochemical properties of urethral smooth muscle in rats of different sexes. These findings may be a basis for the future development of pharmacotherapies for stress urinary incontinence in men. intravesical pressure; external urethral sphincter-electromyography; urethral perfusion pressure; 8-hydroxy-2-(di-n-propylamino)tetralin; WAY-100635; serotonin SEROTONERGIC AGENTS, such as duloxetine, are clinically used to treat stress urinary incontinence (SUI) in women (14). Despite satisfactory results in most female patients, there are few reports regarding the effect of duloxetine on SUI in men. Because the incidence of SUI in men is dramatically lower than in women, SUI is generally considered to be a female issue (27,42). However, epidemiological studies have suggested that men are sometimes severely afflicted with SUI (27) and suffer greater emotional impacts than women (44). Currently, duloxetine has not been approved for treating SUI in men, but the drug has been used off label in some pilot studies; the studies (17,40,48) showed that the drug may produce a marked improvement in men with urinary incontinence.The rat model has now gained great popularity as the main species for developing pharmacologically based treatments of SUI. Effects of a 5-HT receptor agonist on regulatory bladder functions have been extensively investigated in female animals (5,6,15,19,23,28,43). To the best of our knowledge, few studies have explored the role of 5-HT 1A receptors in regulating urethral functions in male rats. In addition, many cases of sexually anatomic and functional dimorphism in the lower urinary trac...

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Urethral Dysfunction in Diabetic Rats

Cited by 87 publications

References 16 publications

Long-term effects of diabetes mellitus on voiding function in a new model of type 2 diabetes mellitus, the Spontaneously Diabetic Torii (SDT) rat

Long-term effects of diabetes mellitus on voiding function in a new model of type 2 diabetes mellitus, the Spontaneously Diabetic Torii (SDT) rat

Neural Control of the Lower Urinary Tract

Sexually dimorphic urethral activity in response to pharmacological activation of 5-HT_1A receptors in the rat

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Urethral Dysfunction in Diabetic Rats

Cited by 87 publications

References 16 publications

Long-term effects of diabetes mellitus on voiding function in a new model of type 2 diabetes mellitus, the Spontaneously Diabetic Torii (SDT) rat

Long-term effects of diabetes mellitus on voiding function in a new model of type 2 diabetes mellitus, the Spontaneously Diabetic Torii (SDT) rat

Neural Control of the Lower Urinary Tract

Sexually dimorphic urethral activity in response to pharmacological activation of 5-HT1A receptors in the rat

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Sexually dimorphic urethral activity in response to pharmacological activation of 5-HT_1A receptors in the rat