| 11. |
- Aronsson, Patrik, 1983, et al.
(author)
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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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In: Neurourology and urodynamics. - : Wiley. - 1520-6777 .- 0733-2467. ; 33:5, s. 550-557
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Journal article (peer-reviewed)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 50mN 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 <2Hz and the maximum response appeared at 10-20Hz, while afferent stimulation had a threshold of 5-10Hz with the maximum response at 40Hz. 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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| 12. |
- Aronsson, Patrik, 1983, et al.
(author)
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Adenosine receptor antagonism suppresses functional and histological inflammatory changes in the rat urinary bladder.
- 2012
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In: Autonomic neuroscience : basic & clinical. - : Elsevier BV. - 1872-7484. ; 171:1-2, s. 49-57
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Journal article (peer-reviewed)abstract
- Cyclophosphamide (CYP) induces an interstitial cystitis-like inflammation. The resulting bladder dysfunction has been associated with increased release of adenosine-5'-triphosphate (ATP), structural bladder wall changes and contractile impairment. Due to the inflammatory modulatory effects of purines it was presently wondered if pre-treatment with P1 and P2 purinoceptor antagonists affect the CYP-induced alterations. Rats were pre-treated with saline or antagonists for five days, and 60h before the in vitro functional examination the rats were administered either saline or CYP. Histological examination revealed CYP-induced bladder wall thickening largely depending on submucosal enlargement, mast cell invasion of the detrusor muscle, increase in muscarinic M5 receptor expression and macrophage migration inhibitory factor (MIF) occurrence in large parts of the urothelium. Functionally, methacholine- and ATP-evoked contractions were smaller in urinary bladders from CYP-treated rats. Pre-treatment with the P2 purinoceptor antagonist suramin and the P1A2B antagonist PSB1115 did not to any great extent affect the CYP-induced changes. The P1A1 antagonist DPCPX, however, abolished the difference of methacholine-evoked contractions between saline- and CYP-treated rats. ATP-evoked contractions were reduced in control after the DPCPX pre-treatment, but not in cystitis. The functional observations for DPCPX were supported by its suppression of CYP-induced submucosal thickening, muscarinic M5 receptor expression and, possibly, detrusor mast cell infiltration and the spread of urothelial MIF occurrence. Thus, P1A1 is an important pro-inflammatory receptor in the acute CYP-induced cystitis and a P1A1 blockade during the initial phase may suppress CYP-induced cystitis. P1A1 purinoceptors seem to regulate contractility in healthy and in inflamed rat urinary bladders.
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| 16. |
- Aronsson, Patrik, 1983, et al.
(author)
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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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In: Neurourology and Urodynamics. - : Wiley. - 0733-2467. ; 34:4, s. 375-380
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Journal article (peer-reviewed)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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| 17. |
- Aronsson, Patrik, 1983, et al.
(author)
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Inhibition of Nitric Oxide Synthase Prevents Muscarinic and Purinergic Functional Changes and Development of Cyclophosphamide-Induced Cystitis in the Rat
- 2014
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In: Biomed research international. - : Hindawi Limited. - 2314-6133 .- 2314-6141.
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Journal article (peer-reviewed)abstract
- Nitric oxide (NO) has pivotal roles in cyclophosphamide-(CYP-) induced cystitis during which mucosal nitric oxide synthase (NOS) and muscarinic M5 receptor expressions are upregulated. In cystitis, urothelial muscarinic NO-linked effects hamper contractility. Therefore we wondered if a blockade of this axis also affects the induction of cystitis in the rat. Rats were pretreated with saline, the muscarinic receptor antagonist 4-DAMP (1mg/kg ip), or the NOS inhibitor L-NAME (30mg/kg ip) for five days. 60 h before the experiments the rats were treated with saline or CYP. Methacholine-, ATP-, and adenosine-evoked responses were smaller in preparations from CYP-treated rats than from saline-treated ones. Pretreatment with 4-DAMP did not change this relation, while pretreatment with L-NAME normalized the responses in the CYP-treated animals. The functional results were strengthened by the morphological observations; 4-DAMP pretreatment did not affect the parameters studied, namely, expression of muscarinic M5 receptors, P1A1 purinoceptors, mast cell distribution, or bladder wall enlargement. However, pretreatment with L-NAME attenuated the differences. Thus, the current study provides new insights into the complex mechanisms behind CYP-induced cystitis. The NO effects coupled to urothelial muscarinic receptors have a minor role in the development of cystitis. Inhibition of NOS may prevent the progression of cystitis.
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| 20. |
- Aronsson, Patrik, 1983, et al.
(author)
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Purinergic impact on urothelial cell proliferation
- 2012
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In: 6th European Congress of Pharmacology. Granda, Spanien, 17-20 juli 2012..
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Conference paper (other academic/artistic)abstract
- Program: http://www.labtamargo.com/CONGRESOS/Congresos-2012/EPHAR-programme.pdf
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