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西洛多辛和他达拉非对自发性高血压大鼠膀胱功能障碍的影响:膀胱血流的可能作用。

Effects of silodosin and tadalafil on bladder dysfunction in spontaneously hypertensive rats: Possible role of bladder blood flow.

机构信息

Departments of, Department of, Pharmacology, Kochi Medical School, Kochi University, Nankoku, Kochi, Japan.

Department of, Pediatrics, Kochi Medical School, Kochi University, Nankoku, Kochi, Japan.

出版信息

Int J Urol. 2020 Mar;27(3):258-265. doi: 10.1111/iju.14171. Epub 2020 Jan 16.

Abstract

OBJECTIVES

To investigate the effects of an alpha1-adrenoceptor antagonist, silodosin, or a phosphodiesterase type 5 inhibitor, tadalafil, on bladder overactivity in spontaneously hypertensive rats.

METHODS

Twelve-week-old male spontaneously hypertensive rats were perorally administered silodosin (100 µg/kg), tadalafil (2 or 10 mg/kg) or vehicle once daily for 6 weeks. Wistar rats were used as normotensive controls and were treated with the vehicle. At 18-weeks-old, the effects of silodosin or tadalafil on blood pressure, bladder blood flow, urodynamic parameters (i.e. micturition frequency, urine output, inter-contraction interval, maximum voiding pressure, single voided volume and post-voiding residual urine volume), and bladder tissue levels of malondialdehyde, interleukin-6 and tumor necrosis factor-alpha were measured.

RESULTS

A significant increase in blood pressure, micturition frequency and bladder tissue levels of malondialdehyde, interleukin-6 and tumor necrosis factor-alpha was noted in spontaneously hypertensive rats. The single voided volume, bladder capacity and bladder blood flow were significantly lower in the spontaneously hypertensive rats than in the Wistar rats. Treatment with silodosin and the higher dose of tadalafil improved the urodynamic parameters, bladder blood flow and bladder tissue levels of malondialdehyde in the spontaneously hypertensive rats without affecting the blood pressure and bladder tissue levels of interleukin-6 and tumor necrosis factor-alpha.

CONCLUSIONS

Treatment with silodosin or tadalafil might improve hypertension-related bladder overactivity, as shown in spontaneously hypertensive rats through an improvement in the bladder blood flow and bladder tissue levels of oxidative stress.

摘要

目的

研究α1-肾上腺素受体拮抗剂西洛多辛或磷酸二酯酶 5 抑制剂他达拉非对自发性高血压大鼠膀胱过度活动的影响。

方法

12 周龄雄性自发性高血压大鼠每天经口给予西洛多辛(100μg/kg)、他达拉非(2 或 10mg/kg)或载体,连续 6 周。Wistar 大鼠作为正常血压对照,并用载体处理。在 18 周龄时,测量西洛多辛或他达拉非对血压、膀胱血流、尿动力学参数(即排尿频率、尿量、收缩间隔、最大排尿压、单次排尿量和排尿后残余尿量)以及膀胱组织丙二醛、白细胞介素-6 和肿瘤坏死因子-α水平的影响。

结果

自发性高血压大鼠血压、排尿频率以及膀胱组织丙二醛、白细胞介素-6 和肿瘤坏死因子-α水平显著升高。与 Wistar 大鼠相比,自发性高血压大鼠的单次排尿量、膀胱容量和膀胱血流明显降低。西洛多辛和较高剂量的他达拉非治疗改善了自发性高血压大鼠的尿动力学参数、膀胱血流和膀胱组织丙二醛水平,而不影响血压和膀胱组织白细胞介素-6 和肿瘤坏死因子-α水平。

结论

西洛多辛或他达拉非治疗可能通过改善膀胱血流和膀胱组织氧化应激水平来改善与高血压相关的膀胱过度活动,这在自发性高血压大鼠中得到了证实。

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