Department of Pharmacy and Biomolecular Sciences, University of Brighton, Brighton, UK.
Centre for Stress and Age-Related Diseases, University of Brighton, Brighton, UK.
Pharmacol Res Perspect. 2020 Feb;8(1):e00564. doi: 10.1002/prp2.564.
Today, monotherapy is the most common pharmacological treatment option for patients suffering from overactive bladder (OAB). Recent reports have indicated potential benefits of combination therapy, using a muscarinic antagonist and a β -adrenoceptor agonist. This may be of particular interest for therapy-resistant patients with OAB and concomitant cystitis. The objective of the current study was to assess how combination therapy affects bladder parameters in health and cystitis and if the efficacy of the drugs can be linked to altered release of nitric oxide (NO). Rats were pretreated with either a combination of the muscarinic antagonist tolterodine and β -selective adrenoceptor agonist mirabegron or saline for 10 days. Forty-eight hours prior to assessing micturition parameters in a metabolic cage, the rats were intraperitoneally injected with cyclophosphamide, causing cystitis, or saline. Urine samples were collected and analyzed for NO content. Bladder contractile properties were assessed in an organ bath setup. Induction of cystitis led to bladder overactivity. Combination therapy normalized bladder parameters. Both induction of cystitis and drug treatment increased the release of NO. The innate contractile properties of the bladder were unaffected by combination therapy. This study demonstrates positive effects of combination drug therapy on symptoms of OAB, possibly indicating it to be a good option for treatment of OAB during concomitant cystitis. It remains to be determined if increased release of NO is crucial for successful pharmacological treatment of bladder overactivity during cystitis.
目前，对于患有膀胱过度活动症（OAB）的患者，单药治疗是最常见的药物治疗选择。最近的报告表明，联合治疗（使用毒蕈碱拮抗剂和β-肾上腺素受体激动剂）可能具有潜在的益处。对于伴有膀胱炎的 OAB 治疗抵抗患者，这可能特别有趣。本研究的目的是评估联合治疗如何影响健康和膀胱炎患者的膀胱参数，以及药物的疗效是否与一氧化氮（NO）释放的改变有关。大鼠用毒蕈碱拮抗剂托特罗定和β-选择性肾上腺素受体激动剂米拉贝隆的组合或生理盐水预处理 10 天。在代谢笼中评估排尿参数之前 48 小时，大鼠腹膜内注射环磷酰胺引起膀胱炎或生理盐水。收集尿液样本并分析 NO 含量。在器官浴装置中评估膀胱收缩特性。膀胱炎的诱导导致膀胱过度活动。联合治疗使膀胱参数正常化。膀胱炎的诱导和药物治疗均增加了 NO 的释放。膀胱的固有收缩特性不受联合治疗的影响。本研究表明联合药物治疗对 OAB 症状有积极影响，这表明它可能是治疗伴有膀胱炎的 OAB 的一种很好的选择。NO 释放增加是否对膀胱炎期间膀胱过度活动的成功药物治疗至关重要仍有待确定。
