Antidiuretic effect of antimuscarinic agents in rat model depends on C-fibre afferent nerves in the bladder.
Antidiuretic effect of antimuscarinic agents in rat model depends on C-fibre afferent nerves in the bladder.
复制标题
抗毒蕈碱药物在大鼠模型中的抗利尿作用取决于膀胱中的 C 纤维传入神经。
DOI：
10.1111/j.1464-410x.2012.11747.x
复制
发表时间：
2013
期刊：
影响因子：
4.5
通讯作者：
Yokoyama O.
中科院分区：
文献类型：
--
作者：
Watanabe N;Akino H;Kurokawa T;Taga M;Yokokawa R;Tanase K;Nagase K;Yokoyama O.
关于这个主题有什么已知的？该研究增加了什么抗胆碱能药物预计可以减轻储存症状以及夜尿症。然而，这种治疗对与夜尿相关的多尿的效果尚不清楚。通过对日本 OAB 患者抗毒蕈碱药物 III 期临床试验数据集的亚组分析，发现咪达那新可改善夜尿，减少夜间多尿。本研究增加了抗毒蕈碱药物通过抑制水导大鼠膀胱中的 C 纤维来减少尿产生的作用和潜在机制。目的评估抗毒蕈碱药物用于减少水负荷大鼠尿产生的效果和潜在机制。受试者和方法每 2 小时使用膀胱造口导管测量雌性 Sprague-Dawley 大鼠的尿产量。在腹水诱导的水负载条件下，研究了抗毒蕈碱药物阿托品、托特罗定和咪达那新对尿产量的影响。注射15mL生理盐水。在抗毒蕈碱剂给药前、给药后2小时和8小时采集血样测定抗利尿激素（ADH）、醛固酮（ALD）、心房钠尿肽（ANP）和脑钠尿肽（BNP）水平。注射树脂毒素（RTX）诱导C纤维传入神经脱敏。南卡罗来纳州或实验前2天膀胱灌注。结果注射15mL生理盐水后2小时尿量增加并达到最大。伊米达那新和托特罗定减少了水负荷大鼠的尿量，但咪达那新治疗组和媒介物治疗组大鼠的ADH、ALD、ANP和BNP水平没有差异。RTX治疗组未发现对尿量的抑制作用。阿托品没有减少尿量。结论这些结果表明抗毒蕈碱剂通过膀胱中的 C 纤维减少尿量；因此，对 C 纤维具有抑制作用的抗毒蕈碱药可能有益于治疗夜间多尿症。
What's known on the subject? and What does the study addAntichollnergic agents are anticipated to diminish storage symptoms, as well as nocturia. Nevertheless, the effect of this treatment on polyuria related to nocturia is not clear. By subgroup analysis of the data set from a phase III clinical trial of antimuscarinic agent for OAB patients in Japan, imidafenacin was found to improve nocturia with a reduction in nocturnal polyuria.This study adds the effects and underlying mechanism of antimuscarinic agents decreasing urine production through inhibition of C‐fibre in the bladder of water‐leaded rats.ObjectiveTo evaluate the effects and underlying mechanisms of antimuscarinic agents used to decrease in urine production in water‐loaded rats.Subjects and MethodsUrine production was measured using a cystostomy catheter in female Sprague–Dawley rats every 2 h.The effect of the antimuscarinic agents atropine, tolterodine and imidafenacin on urine production was investigated under water‐loaded conditions, which were induced by i.p. injection of 15 mL saline.Blood samples were collected to determine the levels of antidiuretic hormone (ADH), aldosterone (ALD), atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) before, and 2 and 8 h after, antimuscarinic agent administration.To induce desensitization of C‐fibre afferent nerves, resiniferatoxin (RTX)was injected s.c. or intravesically 2 days before experiments.ResultsUrine production increased and reached its maximum 2 h after 15 mL saline injection.Imidafenacin and tolterodine decreased urine production in water‐loaded rats, but ADH, ALD, ANP and BNP levels were not different between imidafenacin‐treated and vehicle‐treated rats.The inhibitory effect on urine production was not found in RTX‐treated rats.Atropine did not reduce urine production.ConclusionThese results suggest that antimuscarinic agents decrease urine volume through C‐fibres in the bladder; thus, antimuscarinics with inhibitory effects on C‐fibres could be beneficial for nocturia with nocturnal polyuria.