Effects of Mk-801 on Bladder Overactivity in Rats With Cerebral Infarction

Yokoyama, Osamu; Ishiura, Yoshiyuki; Komatsu, Kazuto; Mita, Eiko; Nakamura, Yasuo; Kunimi, Kazuto; Morikawa, Kouji; Namiki, Mikio

doi:10.1016/s0022-5347(01)63986-7

Cited by 32 publications

(12 citation statements)

References 23 publications

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“…an increase in ICI, in urethane-anaesthetized rats, suggesting that NO has excitatory and inhibitory mechanisms, and that the excitatory mechanisms controlling bladder function are unmasked by urethane anaesthesia. These responses were consistent with the findings that MK-801, a N-methyl-D -aspartate (NMDA) receptor antagonist, decreased the BC in awake rats but increased the BC in urethaneanaesthetized rats [11,12]. The activation of NMDA receptors in the CNS initiates an influx of Ca 2 + , inducing Ca 2 + -dependent intracellular processes, while NOS is a Ca 2 + /calmodulindependent enzyme that is stimulated by the activation of NMDA receptors [13].…”

Section: Discussionsupporting

confidence: 87%

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Effects of anaesthesia on the nitrergic pathway during the micturition reflex in rats

Masuda

Ogawa²,

Kihara

et al. 2007

BJU International

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RESULTSL-NAME injected i.v. decreased the intercontraction interval (ICI) in the awake but increased it in the anaesthetized rats. L-NAME injected i.t. increased the ICI in both states and these effects were not apparent after pre-treatment with resiniferatoxin. L-NAME injected i.c.v. decreased the ICI in the awake but increased i.t. in the anaesthetized rats. Intravesical L-NAME decreased the ICI in the awake but not in the anaesthetized rats. L-NAME administered i.v., but not i.t. or i.c.v., increased bladder contraction during CMG. Under isovolumetric conditions, L-NAME administered i.v., but not i.t. or i.c.v., reduced the urethral relaxation without changing bladder contraction. CONCLUSIONSThese results indicate that spinal NO release facilitates the mechanoceptive C-fibres, and this facilitatory effect is masked by supraspinal (possibly forebrain) and local inhibitory effects of NO during the micturition reflex in awake rats. Urethane seems to inhibit the supraspinal and local inhibitory effects of NO, resulting in unmasking the facilitatory effect of NO in the spinal cord and brain stem. During the voiding phase, urethral relaxation depends on the peripheral but not the central NO system.

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Section: Discussionsupporting

confidence: 87%

“…It was proposed that two glutamatergic pathways regulate bladder activity. The first is an inhibitory pathway that originates from the forebrain, and the second is an excitatory pathway located at more caudal sites, possibly in the brainstem or in the spinal cord [12,16]. In the present study, i.c.v.…”

Section: Discussionmentioning

confidence: 95%

Effects of anaesthesia on the nitrergic pathway during the micturition reflex in rats

Masuda

Ogawa²,

Kihara

et al. 2007

BJU International

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“…It has been speculated that two glutamatergic pathways regulate bladder activity. The first is an inhibitory pathway that originates from the forebrain and the second is an excitatory pathway located at more caudal sites, possibly in the brainstem or in the spinal cord 28 . It seems likely that activation of NMDA receptor‐linked NOS in the spinal cord and the brain is involved in the micturition reflex in normal and pathophysiological conditions.…”

Section: Central Role Of No In the Regulation Of The Lower Urinarymentioning

confidence: 99%

Significance of Nitric Oxide and its Modulation Mechanisms in Micturition Disorders

Masuda

Yano

Ichiyanagi

et al. 2009

LUTS

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Nitric oxide (NO) pathway is of critical importance in the physiological regulation of micturition reflex. NO released from urothelium and suburothelium depresses afferent micturition pathway, while in the central nervous system NO has dual effects on afferent pathway; i.e, excitatory effect in the spinal cord and brain stem and inhibitory effect in the forebrain. Elevated endogenous NO synthase (NOS) inhibitors and increased arginase activity in the lower urinary tracts contribute to NO deficiency, leading to impairement of NO‐mediated relaxations and excitation of different pathway. Therefore, manipulation of endogenous NOS inhibitors and arginase may be new targets of micturition disorders.

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“…Some studies focusing on glutamatergic receptors in relation to micturition re ex (16, 18-20, 23, 33-35) have found that at least two glutamatergic systems in the brain are involved in the control of the micturition re ex pathway. One glutamatergic system, which has a low sensitivity to dizocilpine, originates in the brain stem and mediates excitatory control of voiding (19,34). The other system, which is more sensitive to dizocilpine, originates in the forebrain and activates an inhibitory mechanism that controls bladder capacity.…”

Section: Therapeutic Potential Of Central Dopaminergic and Gabaergic mentioning

confidence: 99%

Overactive Bladder - Experimental Aspects

Yokoyama

Komatsu

Ishiura

et al. 2002

Scandinavian Journal of Urology and Nephrology

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Scand J Urol Nephrol Suppl 210: 59-64, 2002 Supra-pontine lesions resulting from neurological disorders such as vascular disease, Parkinson's disease, or Alzheimer type senile dementia lead to an increase in bladder activity. This is due in part to the removal at the cortical inhibitory control of the micturition center in the brain stem -i.e. the pontine micturition center (PMC) -and in part to facilitation of excitatory control. These inhibitory or excitatory controls consist of several neurotransmitter systems, including glutamate, dopamine, gaminobutyric acid (GABA), and acetylcholine. Bladder overactivity caused by cerebral infarction is mediated by upregulation of N-methyl-D-aspartate (NMDA) glutamatergic and D2 dopaminergic excitatory mechanisms, and by downregulation of NMDA glutamatergic and M1 muscarinic inhibitory mechanisms in the brain. Bladder overactivity associated with Parkinson's disease is reportedly induced by a loss of input to the D1 dopaminergic receptor. Furthermore, bladder overactivity caused by Alzheimer type dementia is thought to be mediated by downregulation of M1 muscarinic inhibitory mechanisms. Development of bladder overactivity following cerebral infarction is mediated by activation of the NMDA receptor and accompanied by an increase in c-fos, zif268 and COX-2 mRNA expression in the dorsal pontine tegmentum.

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Effects of Mk-801 on Bladder Overactivity in Rats With Cerebral Infarction

Abstract: Results in urethane anesthetized rats indicate that NMDA glutamatergic transmission is important in the overactivity of the bladder following a cerebral infarction. This model is useful in studying the neurogenic voiding dysfunction observed in patients with cerebrovascular disease.

Cited by 32 publications

References 23 publications

Effects of anaesthesia on the nitrergic pathway during the micturition reflex in rats

Effects of anaesthesia on the nitrergic pathway during the micturition reflex in rats

Significance of Nitric Oxide and its Modulation Mechanisms in Micturition Disorders

Overactive Bladder - Experimental Aspects

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