Voiding effects mediated by α2-adrenoceptors in the anaesthetized male rat.
OBJECTIVE
To study the role of α(2)-adrenoceptors (α(2)-AR) in micturition of anaesthetized male rats, with specific focus on the effects on the electrical activity (by electromyography, EMG) of the rhabdosphincter, and actual urinary flow rate, as the effects mediated by α(2)-ARs on sphincter activity and urethral pressures have not been established.


METHODS
Adult anaesthetized male Noble rats were used; intravesical pressure, rhabdosphincter EMG and urinary flow rate from the distal urethra were recorded. After baseline recordings, an α(2)-AR agonist (dexmedetomidine, DEX) or α(2)-AR antagonist (atipamezole), were injected intravenously.


RESULTS
DEX treatment significantly decreased the maximum bladder pressure and urinary flow rate, and the amplitude of rhabdosphincter EMG was significantly reduced. Intraluminal pressure high-frequency oscillations, usually observed during rat voiding were abolished. The effects of DEX were fully reversed within 31 min. Atipamezole treatment significantly increased actual urinary flow rates and rhabdosphincter EMG amplitude, but the number of times flow was interrupted was increased during the voiding cycle, leading to increased overall micturition time.


CONCLUSIONS
Stimulation and blockade of α(2)-ARs have a significant effect on lower urinary tract function. If the data from this rat model are also valid in humans, a study of the effects of atipamezole on urethral sphincter activity and urethral pressures in humans would be of interest, and might show therapeutic potential of the drug.
Department of Pharmacology, Drug Development and Therapeutics, and Turku Centre for Disease Modelling, Institute of Biomedicine, University of Turku, Turku, Finland. tostren@utu.fi
Tomi
T
Streng
Risto
R
Santti
Karl-Erik
KE
Andersson
D058647:Adrenergic alpha-2 Receptor Agonists / Q000494:pharmacology*; D058669:Adrenergic alpha-2 Receptor Antagonists / Q000494:pharmacology*; D000758:Anesthesia; D000818:Animals; D020927:Dexmedetomidine / Q000494:pharmacology*; D007093:Imidazoles / Q000494:pharmacology*; D008297:Male; D051381:Rats; D014551:Urinary Tract / Q000187:drug effects; D014554:Urination / Q000187:drug effects* / Q000502:physiology; D014563:Urodynamics / Q000187:drug effects* / Q000502:physiology
D058647:Adrenergic alpha-2 Receptor Agonists; D058669:Adrenergic alpha-2 Receptor Antagonists; D007093:Imidazoles; C050701:atipamezole; D020927:Dexmedetomidine