Antidiuretic effect of antimuscarinic agents in rat model depends on C-fibre afferent nerves in the bladder

作者：Watanabe Nozomu^*; Akino Hironobu; Kurokawa Tetsuyuki; Taga Minekatu; Yokokawa Ryusei; Tanase Kazuya; Nagase Keiko; Yokoyama Osamu

来源：BJU International, 2013, 112(1): 131-136.

DOI：10.1111/j.1464-410X.2012.11747.x

• antimuscarinic
• antidiuretic
• C-fibre
• bladder
• urine production

What%26apos;s known on the subject? and What does the study add? Antichollnergic 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. Objective To evaluate the effects and underlying mechanisms of antimuscarinic agents used to decrease in urine production in water-loaded rats. Subjects and Methods Urine production was measured using a cystostomy catheter in female Sprague-Dawley rats every 2h. 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 15mL 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 8h after, antimuscarinic agent administration. To induce desensitization of C-fibre afferent nerves, resiniferatoxin (RTX)was injected s.c. or intravesically 2 days before experiments. Results Urine production increased and reached its maximum 2h after 15mL 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. Conclusion These 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.

• 出版日期2013-7