Therapeutic effects of silodosin and urapidil on underactive bladder associated with diabetic cystopathy

IF 1.5 4区医学 Q3 UROLOGY & NEPHROLOGY LUTS: Lower Urinary Tract Symptoms Pub Date : 2022-09-04 DOI:10.1111/luts.12462

Saori Yonekubo-Awaka, Motohiro Tezuka, Satoshi Tatemichi, Hiroo Takeda

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Abstract

Objectives

Pharmacological treatment options for underactive bladder (UAB) syndrome are limited. Urapidil is the only alpha₁-adrenoceptor (AR) antagonist that can be used for urinary disorders in women in some countries. However, no studies have directly verified the effects of alpha₁-AR antagonists on the female urethra and UAB-like dysfunctions. We investigated the effects of silodosin (alpha_1A-AR antagonist) and urapidil (nonselective alpha₁-AR antagonist) on the voiding function in female rats with diabetes mellitus (DM).

Methods

Changes in intraurethral pressure (IUP) induced by midodrine (alpha₁-AR agonist) and mean blood pressure (MBP) were continuously measured in normal female rats to verify the pharmacological profiles of the drugs. To establish a DM model, rats were administered streptozotocin (STZ; 50 mg/kg, intravenous). Eight weeks after STZ administration, drugs were subcutaneously delivered through an osmotic pump. Four weeks after drug administration, emptied bladder blood flow (BBF), intravesical pressure, and the micturition volume were measured.

Results

Both silodosin and urapidil inhibited the midodrine-induced increase in IUP and decreased MBP in a dose-dependent manner. Silodosin had a more substantial effect on the lower urinary tract than on MBP. Twelve weeks after STZ administration, DM rats exhibited UAB-like dysfunction (increased bladder capacity/bladder weight and residual volume and decreased bladder voided efficiency) and decreased BBF. Both drug treatments controlled this dysfunction.

Conclusions

Alpha₁-AR antagonists induced dose-dependent urethral relaxation in female rats. These drugs ameliorated UAB-like dysfunction in STZ-induced DM rats. In addition, alpha_1A-AR antagonists such as silodosin, which have limited effects on blood pressure, appear to be useful for treating UAB.

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西洛多辛和乌拉地尔治疗糖尿病性膀胱病变伴膀胱活动不足的疗效观察

目的膀胱活动不足综合征(UAB)的药物治疗选择有限。在一些国家，乌拉地尔是唯一可用于女性泌尿系统疾病的α - 1肾上腺素受体(AR)拮抗剂。然而，目前还没有研究直接证实alpha1-AR拮抗剂对女性尿道和uab样功能障碍的影响。研究西洛多辛(α α - ar拮抗剂)和乌拉地尔(非选择性α 1- ar拮抗剂)对雌性糖尿病大鼠排尿功能的影响。方法连续测定正常雌性大鼠经内压(IUP)和平均血压(MBP)的变化，验证药物的药理作用。为了建立DM模型，大鼠注射链脲佐菌素(STZ);50mg /kg，静脉注射)。STZ给药8周后，通过渗透泵皮下给药。给药4周后，测定膀胱空血流量(BBF)、膀胱内压、排尿量。结果西洛多辛和乌拉地尔均能抑制米多卡因诱导的IUP升高和MBP降低，且呈剂量依赖性。西洛多辛对下尿路的影响比对MBP的影响更显著。STZ给药12周后，DM大鼠表现出uab样功能障碍(膀胱容量/膀胱重量和残余体积增加，膀胱排尿效率降低)和血流量减少。两种药物治疗都控制了这种功能障碍。结论α 1- ar拮抗剂可诱导雌性大鼠剂量依赖性尿道松弛。这些药物改善了stz诱导的糖尿病大鼠uab样功能障碍。此外，α - 1a - ar拮抗剂，如西洛多辛，对血压的影响有限，似乎对治疗UAB有用。

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来源期刊

LUTS: Lower Urinary Tract Symptoms UROLOGY & NEPHROLOGY-

CiteScore

3.00

自引率

7.70%

发文量

审稿时长

>12 weeks

期刊介绍： LUTS is designed for the timely communication of peer-reviewed studies which provides new clinical and basic science information to physicians and researchers in the field of neurourology, urodynamics and urogynecology. Contributions are reviewed and selected by a group of distinguished referees from around the world, some of whom constitute the journal''s Editorial Board. The journal covers both basic and clinical research on lower urinary tract dysfunctions (LUTD), such as overactive bladder (OAB), detrusor underactivity, benign prostatic hyperplasia (BPH), bladder outlet obstruction (BOO), urinary incontinence, pelvic organ prolapse (POP), painful bladder syndrome (PBS), as well as on other relevant conditions. Case reports are published only if new findings are provided. LUTS is an official journal of the Japanese Continence Society, the Korean Continence Society, and the Taiwanese Continence Society. Submission of papers from all countries are welcome. LUTS has been accepted into Science Citation Index Expanded (SCIE) with a 2011 Impact Factor.