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- Aronsson, Patrik, 1983, et al.
(författare)
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A novel in situ urinary bladder model for studying afferent and efferent mechanisms in the micturition reflex in the rat.
- 2014
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Ingår i: Neurourology and urodynamics. - : Wiley. - 1520-6777 .- 0733-2467. ; 33:5, s. 550-557
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: The search for new animal models to investigate both efferent and afferent levels of the micturition reflex, to better understand urinary dysfunctions, is of great importance. Therefore in this study we developed and characterized, by comparisons with a conventional whole bladder model, a novel in situ model. METHODS: The urinary bladder was carefully prepared and separated, via a midline incision, into two halves all the way to the urethra in pentobarbitone and medetomidine anesthetized male rats. The separated bladder halves (with no direct connection) were immobilized with ligatures to the underlying tissue. The tension could thereafter be recorded at one side, while the other half was occasionally stretched in order to evoke an afferent signal. Also, injections of ATP and methacholine and electric nerve stimulation were employed. RESULTS: Ipsilateral stretch of 30 and 50 mN induced a force-dependent contractile response on the contralateral side. Moreover, electrical stimulation of efferent pelvic nerve fibers, and intravenous injections of methacholine and ATP, evoked dose-dependent contractions, resembling responses observed in the whole bladder model. Here, the threshold frequency at electrical stimulation of the efferent fibers was <2 Hz and the maximum response appeared at 10-20 Hz, while afferent stimulation had a threshold of 5-10 Hz with the maximum response at 40 Hz. CONCLUSIONS: In the current study we show that stimulation of afferents at one side of the bladder induces, via impulses from the central nervous system, contractions from the other side. This novel model enables quantitative comparisons of changes occurring within the micturition reflex arc in bladder disorders.
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| 2. |
- Chakrabarty, Basu, et al.
(författare)
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Nitric oxide signaling pathways in the normal and pathological bladder: Do they provide new pharmacological pathways?—ICI-RS 2023
- 2023
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Ingår i: Neurourology and Urodynamics. - 0733-2467 .- 1520-6777.
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Forskningsöversikt (refereegranskat)abstract
- Aims: The nitric oxide (NO•)/soluble guanylate cyclase/cyclic-GMP (cGMP) signaling pathway is ubiquitous and regulates several functions in physiological systems as diverse as the vascular, nervous, and renal systems. However, its roles in determining normal and abnormal lower urinary tract functions are unclear. The aim was to identify potential therapeutic targets associated with this pathway to manage lower urinary tract functional disorders. Methods: This review summarizes a workshop held under the auspices of ICI-RS with a view to address these questions. Results: Four areas were addressed: NO• signaling to regulate neurotransmitter release to detrusor smooth muscle; its potential dual roles in alleviating and exacerbating inflammatory pathways; its ability to act as an antifibrotic mediator; and the control by nitrergic nerves of lower urinary tract vascular dynamics and the contractile performance of muscular regions of the bladder wall. Central to much of the discussion was the role of the NO• receptor, soluble guanylate cyclase (sGC) in regulating the generation of the enzyme product, the second messenger cGMP. The redox state of sGC is crucial in determining its enzymic activity and the role of a class of novel agents, sGC activators, to optimize activity and to potentially alleviate the consequences of lower urinary tract disorders was highlighted. In addition, the consequences of a functional relationship between nitrergic and sympathetic nerves to regulate vascular dynamics was discussed. Conclusions: Several potential NO•-dependent drug targets in the lower urinary tract were identified that provide the basis for future research and translation to clinical trials.
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| 3. |
- Aronsson, Patrik, 1983, et al.
(författare)
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Cyclophosphamide-induced alterations of the micturition reflex in a novel in situ urinary bladder model in the anesthetized rat
- 2015
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Ingår i: Neurourology and Urodynamics. - : Wiley. - 0733-2467. ; 34:4
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Tidskriftsartikel (refereegranskat)abstract
- Aims: Cyclophosphamide-induced cystitis alterations have been reported to occur both at efferent and afferent level in the micturition reflex arc. In particular, the stretching of the bladder wall causing urothelial release of ATP has been proposed as one of the pivotal mechanisms causing these alterations. To evaluate functional changes at efferent and afferent levels of the micturition reflex following cyclophosphamide treatment we have applied a novel in situ half bladder rat model. Methods: Male Sprague-Dawley rats were treated with either saline or cyclophosphamide (100mg/kg), and stretch-, electric-, methacholine-, and ATP-induced responses were thereafter measured at 60-72hr postinjection under pentobarbitone anesthesia. In the novel in situ half bladder model, the urinary bladder was prepared via a midline incision, where the two halves were separated all the way to the urethra as previously described. Results: Following bladder stretch of 30-80mN, of the half that was not used for tension measurement, the cyclophosphamide-treated animals evoked significant two- to threefold larger contractile responses as compared to saline-treated control animals. A sensitization of the afferent arm was shown in cyclophosphamide-treated animals, since afferent stimulation evoked similar responses as in control animals despite that the efferent pelvic nerve stimulation displayed a lower contraction-frequency relationship in cyclophosphamide-treated animals. Atropine reduced the stretch(reflex)-evoked contraction by up to 50% in control and 75-80% in cyclophosphamide-treated rats. Subsequent addition of PPADS further reduced the contractions. Conclusion: The micturition reflex response is increased following cyclophosphamide-induced cystitis, as compared to control. The likely cause is sensitization at mechanosensor level in the micturition arc, which overrides the decrement of the efferent cholinergic effects. © 2014 Wiley Periodicals, Inc.
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| 4. |
- Kanai, A., et al.
(författare)
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New therapeutic targets to prevent benign prostatic enlargement and symptomatic progression to benign prostatic obstruction-ICI-RS 2023
- 2023
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Ingår i: Neurourology and Urodynamics. - 0733-2467.
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Tidskriftsartikel (refereegranskat)abstract
- AimsBenign prostatic enlargement (BPE) can impact lower urinary tract function due to its potential progression to benign prostatic obstruction (BPO). Treatment options include removal of the obstruction by surgery or through use of therapeutics designed to slow growth or reduce tissue stress imposed by muscular stromal components. Inflammation and development of fibrosis can also raise intrinsic tissue stress within the gland, further impacting obstruction. Outflow tract obstruction can also impact emission and ejaculation if the obstruction persists.MethodsThis review summarizes an ICI-RS think tank considering novel drug treatments that might address BPO caused by progressive development of BPE, as well as manage decompensation changes to bladder function.ResultsTopics included recent advances in our understanding of pathological changes occurring to the prostate and other lower urinary tract tissues during progressive development of BPE, and how prevention or reversal might benefit from the identification of novel drug targets. These included contractile properties of prostatic tissues, the impact of BPE and its effects on bladder function, the deposition of intramural fibrotic tissue with protracted BPO, the role of inflammation in the development of BPE and its progression to BPO. In particular, we discussed current therapeutic options for treating BPE/BPO, and new therapeutic targets, what they treat and their advantage over current medications.ConclusionSeveral new drug targets were identified, including soluble guanylate cyclase (sGC), the receptor for nitric oxide (NO center dot), and sGC activators that promotes sGC-mediated cGMP production when sGC is inactivated and unresponsive to NO center dot.
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