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研究辛多司汀和萘哌地尔治疗自发性高血压大鼠膀胱功能障碍的作用。

Characterization of silodosin and naftopidil in the treatment of bladder dysfunction in the spontaneously hypertensive rat.

机构信息

Division of Molecular Pharmacology, Tottori University School of Medicine, Yonago, Japan.

出版信息

Neurourol Urodyn. 2013 Apr;32(4):393-8. doi: 10.1002/nau.22297. Epub 2012 Aug 20.

Abstract

PURPOSE

As increasing evidence suggest that α(1)-blockers prevent benign prostatic hyperplasia related overactive bladder and nocturia in the human, we investigated the effects of silodosin and naftopidil on hypertension-related bladder dysfunction in the spontaneously hypertensive rat (SHR) model.

MATERIALS AND METHODS

Twelve-week-old male SHRs received no treatment or treatment with silodosin (100 µg/kg, p.o.) or naftopidil (10 or 30 mg/kg, p.o.) once daily for 6 weeks. Wistar rats were used as normotensive controls. After 6-week treatment, voiding functions were estimated by metabolic cages (dark- and light-cycle separately) and cystometric studies. Furthermore, the bladder blood flow (BBF) was measured employing the hydrogen clearance method.

RESULTS

SHRs showed significant increases in micturition frequency, and decreases in BBF and single voided volume in both metabolic cages and cystometrograms compared to the Wistar group. Treatment with silodosin normalized the decreased BBF, and treatment with naftopidil increased the BBF in a dose-dependent manner in the SHR group. Although treatment with silodosin and the high dose of naftopidil significantly inhibited micturition frequency in one day, only treatment with the high dose of naftopidil significantly inhibited micturition frequency and urine production in the light-cycle compared to the non-treated SHRs. Although treatment with silodosin and the high dose of naftopidil significantly increased single voided volume, only treatment with silodosin significantly inhibited non-voiding contractions in the cystometrgrams.

CONCLUSION

Our data suggest that both silodosin and naftopidil improve hypertension-related bladder dysfunction in the SHR, and naftopidil but not silodosin improves urinary frequency in the light-cycle due to inhibition of urine production.

摘要

目的

越来越多的证据表明,α1-受体阻滞剂可预防良性前列腺增生相关的膀胱过度活动症和夜尿症,因此我们研究了西洛多辛和萘哌地尔对自发性高血压大鼠(SHR)模型中高血压相关膀胱功能障碍的影响。

材料与方法

12 周龄雄性 SHR 大鼠分别接受未治疗或西洛多辛(100μg/kg,po)或萘哌地尔(10 或 30mg/kg,po)治疗,每天 1 次,共 6 周。Wistar 大鼠作为正常血压对照组。治疗 6 周后,通过代谢笼(暗周期和亮周期分别)和膀胱测压研究评估排尿功能。此外,采用氢清除法测量膀胱血流(BBF)。

结果

与 Wistar 组相比,SHR 大鼠的排尿频率明显增加,BBF 和单次排尿量明显减少,无论是在代谢笼还是在膀胱测压研究中。西洛多辛治疗可使降低的 BBF 恢复正常,而萘哌地尔治疗可使 SHR 组的 BBF 呈剂量依赖性增加。尽管西洛多辛和萘哌地尔高剂量治疗均可显著抑制一天内的排尿频率,但只有萘哌地尔高剂量治疗可显著抑制与未治疗 SHR 相比的亮周期内的排尿频率和尿量。尽管西洛多辛和萘哌地尔高剂量治疗均可显著增加单次排尿量,但只有西洛多辛治疗可显著抑制膀胱测压研究中的非排尿收缩。

结论

我们的数据表明,西洛多辛和萘哌地尔均可改善 SHR 的高血压相关膀胱功能障碍,而萘哌地尔而非西洛多辛可通过抑制尿量来改善亮周期内的排尿频率。

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