Abstract
Purpose
Since it has not been established whether there is an effect on voiding exerted by direct stimulation or blockade of α2-adrenoceptors in the bladder and urethra, MK-467, a peripherally acting α2-adrenoceptor antagonist not penetrating into the CNS, was used to test whether part of the voiding effects of systemically given α2-adrenoceptor agonists is peripheral.
Methods
Urodynamic recordings from 27 conscious male adult C57/Bl J-strain mice were performed. After vehicle (saline) administration, two groups of animals were treated first with the selective α2-adrenoceptor agonist dexmedetomidine (Dex) and then with the selective α2-adrenoceptor antagonists atipamezole (Ati) or MK-467. Two other groups were first treated with Ati or MK-467 and then with Dex.
Results
Treatment with vehicle or α2-adrenoceptor antagonists alone did not affect micturition parameters. All animals treated first with Dex-developed overflow incontinence. Treatment with Ati after Dex reversed almost totally the effects of Dex on all voiding parameters, but treatment with MK-467 after Dex showed no detectable improvement. Treatment with Dex after Ati had no effect on any voiding parameter except maximal pressure. When mice were treated with Dex after MK-467, overflow incontinence was produced in seven of eight animals studied.
Conclusions
The absence of functionally relevant peripheral effects on voiding mediated via α2-adrenoceptors is supported by the finding that neither Ati nor MK-467 alone had any effect on micturition parameters and by the inability of MK-467 to inhibit the effects of Dex, suggesting that the relevant Dex effects were exerted within the CNS.
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Conflict of interest
KEA is currently advisor to: Allergan, Astellas and Ferring. The other authors have no conflict of interests.
Ethical standard
The Animal Care Organization and University Ethical Committee of Turku University approved the study protocol. The mice were handled in accordance with the institutional animal care policies of the University of Turku and in accordance with the European Union Directive and with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments. All authors have given their informed consent prior to their inclusion in the study.
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Aro, E., Bastman, S., Andersson, KE. et al. Is there a peripheral site of action contributing to the voiding effects of α2-adrenoceptor agonists and antagonists?. World J Urol 33, 433–440 (2015). https://doi.org/10.1007/s00345-014-1336-z
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DOI: https://doi.org/10.1007/s00345-014-1336-z