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麻醉雄性大鼠中α2-肾上腺素能受体介导的排尿作用。

Voiding effects mediated by α2-adrenoceptors in the anaesthetized male rat.

机构信息

Department of Pharmacology, Drug Development and Therapeutics, and Turku Centre for Disease Modelling, Institute of Biomedicine, University of Turku, Turku, Finland.

出版信息

BJU Int. 2010 Nov;106(10):1546-9. doi: 10.1111/j.1464-410X.2010.09228.x.

DOI:10.1111/j.1464-410X.2010.09228.x
PMID:20151962
Abstract

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.

MATERIALS AND 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.

CONCLUSION

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.

摘要

目的

研究麻醉雄性大鼠排尿过程中α(2)-肾上腺素能受体(α(2)-AR)的作用,特别关注α(2)-AR 对逼尿肌电活动(肌电图,EMG)和实际尿流率的影响,因为 α(2)-AR 对括约肌活动和尿道压力的影响尚未确定。

材料和方法

使用成年麻醉雄性 Noble 大鼠;记录膀胱内压、逼尿肌 EMG 和远端尿道的尿流率。在基线记录后,静脉内注射 α(2)-AR 激动剂(右美托咪定,DEX)或 α(2)-AR 拮抗剂(阿替美唑)。

结果

DEX 处理显著降低最大膀胱压力和尿流率,逼尿肌 EMG 幅度明显降低。在大鼠排尿过程中通常观察到的腔内压力高频振荡被消除。DEX 的作用在 31 分钟内完全逆转。阿替美唑处理显著增加实际尿流率和逼尿肌 EMG 幅度,但在排尿周期中增加了中断次数,导致总排尿时间增加。

结论

刺激和阻断 α(2)-AR 对下尿路功能有显著影响。如果该大鼠模型的数据在人类中也是有效的,那么研究阿替美唑对人类尿道括约肌活动和尿道压力的影响将是有趣的,并且可能显示出该药物的治疗潜力。

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