{"title":"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","authors":"Saori Yonekubo-Awaka, Motohiro Tezuka, Satoshi Tatemichi, Hiroo Takeda","doi":"10.1111/luts.12462","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <h3> Objectives</h3>\n \n <p>Pharmacological treatment options for underactive bladder (UAB) syndrome are limited. Urapidil is the only alpha<sub>1</sub>-adrenoceptor (AR) antagonist that can be used for urinary disorders in women in some countries. However, no studies have directly verified the effects of alpha<sub>1</sub>-AR antagonists on the female urethra and UAB-like dysfunctions. We investigated the effects of silodosin (alpha<sub>1A</sub>-AR antagonist) and urapidil (nonselective alpha<sub>1</sub>-AR antagonist) on the voiding function in female rats with diabetes mellitus (DM).</p>\n </section>\n \n <section>\n \n <h3> Methods</h3>\n \n <p>Changes in intraurethral pressure (IUP) induced by midodrine (alpha<sub>1</sub>-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.</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>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.</p>\n </section>\n \n <section>\n \n <h3> Conclusions</h3>\n \n <p>Alpha<sub>1</sub>-AR antagonists induced dose-dependent urethral relaxation in female rats. These drugs ameliorated UAB-like dysfunction in STZ-induced DM rats. In addition, alpha<sub>1A</sub>-AR antagonists such as silodosin, which have limited effects on blood pressure, appear to be useful for treating UAB.</p>\n </section>\n </div>","PeriodicalId":18028,"journal":{"name":"LUTS: Lower Urinary Tract Symptoms","volume":null,"pages":null},"PeriodicalIF":1.5000,"publicationDate":"2022-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Therapeutic effects of silodosin and urapidil on underactive bladder associated with diabetic cystopathy\",\"authors\":\"Saori Yonekubo-Awaka, Motohiro Tezuka, Satoshi Tatemichi, Hiroo Takeda\",\"doi\":\"10.1111/luts.12462\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div>\\n \\n \\n <section>\\n \\n <h3> Objectives</h3>\\n \\n <p>Pharmacological treatment options for underactive bladder (UAB) syndrome are limited. Urapidil is the only alpha<sub>1</sub>-adrenoceptor (AR) antagonist that can be used for urinary disorders in women in some countries. However, no studies have directly verified the effects of alpha<sub>1</sub>-AR antagonists on the female urethra and UAB-like dysfunctions. We investigated the effects of silodosin (alpha<sub>1A</sub>-AR antagonist) and urapidil (nonselective alpha<sub>1</sub>-AR antagonist) on the voiding function in female rats with diabetes mellitus (DM).</p>\\n </section>\\n \\n <section>\\n \\n <h3> Methods</h3>\\n \\n <p>Changes in intraurethral pressure (IUP) induced by midodrine (alpha<sub>1</sub>-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.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Results</h3>\\n \\n <p>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.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Conclusions</h3>\\n \\n <p>Alpha<sub>1</sub>-AR antagonists induced dose-dependent urethral relaxation in female rats. These drugs ameliorated UAB-like dysfunction in STZ-induced DM rats. In addition, alpha<sub>1A</sub>-AR antagonists such as silodosin, which have limited effects on blood pressure, appear to be useful for treating UAB.</p>\\n </section>\\n </div>\",\"PeriodicalId\":18028,\"journal\":{\"name\":\"LUTS: Lower Urinary Tract Symptoms\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":1.5000,\"publicationDate\":\"2022-09-04\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"LUTS: Lower Urinary Tract Symptoms\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1111/luts.12462\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"UROLOGY & NEPHROLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"LUTS: Lower Urinary Tract Symptoms","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1111/luts.12462","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"UROLOGY & NEPHROLOGY","Score":null,"Total":0}
Therapeutic effects of silodosin and urapidil on underactive bladder associated with diabetic cystopathy
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 (alpha1A-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, alpha1A-AR antagonists such as silodosin, which have limited effects on blood pressure, appear to be useful for treating UAB.
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.
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