Differences between young and aged rats in voiding frequency and detrusor muscle serotonergic contraction

Asaki Takanashi; Azuki Sakai-Saito; Tsuyoshi Hattori; Sumika Kanno-Saito; Yumi Katano; Takao Okada

doi:10.1016/j.exger.2019.110642

Differences between young and aged rats in voiding frequency and detrusor muscle serotonergic contraction

Exp Gerontol. 2019 Sep:124:110642. doi: 10.1016/j.exger.2019.110642. Epub 2019 Jun 27.

Authors

Asaki Takanashi¹, Azuki Sakai-Saito², Tsuyoshi Hattori³, Sumika Kanno-Saito², Yumi Katano⁴, Takao Okada⁵

Affiliations

¹ Faculty of Health Care and Nursing, Juntendo University, Chiba, Japan; Division of Medical Education, Juntendo University School of Medicine, Tokyo, Japan. Electronic address: atakana@juntendo.ac.jp.
² Division of Theoretical Nursing and Pathophysiology, Yamagata University School of Medicine, Yamagata, Japan.
³ Department of Medical Affairs, Asahi Kasei Pharma Corporation, Tokyo, Japan. Electronic address: hattori.tg@om.asahi-kasei.co.jp.
⁴ Yamagata University, Yamagata, Japan. Electronic address: ykatano@med.id.yamagata-u.ac.jp.
⁵ Division of Medical Education, Juntendo University School of Medicine, Tokyo, Japan. Electronic address: tokada@juntendo.ac.jp.

PMID: 31255734
DOI: 10.1016/j.exger.2019.110642

Abstract

Introduction: The involvement of serotonin (5-HT) in increased lower urinary tract symptoms in aging is unclear. We sought to compare voiding function and 5-HT induced detrusor contraction between young and aged rats.

Methods: This study used young (2- to 3-month-old) and aged (26- to 30-month-old) male Fischer 344 rats. 1. Rats were housed in individual metabolic cages, and then the total volume of urination, volume per micturition, voiding frequency, and voiding interval were analyzed. 2. Using urinary bladder body strips, developed tension was recorded after cumulative addition of 5-HT (1-100 nM) in the absence or presence of tetrodotoxin (1 μM), and in the presence of tetrodotoxin with ketanserin (0.3-3 μM) or naftopidil (1 and 3 μM). We examined the effects of atropine, ketanserin, and naftopidil on electrical field stimulation (EFS)-induced contraction.

Results: 1. Compared to young rats, aged rats exhibited decreased voiding frequency and increased volume per micturition, but total volume of urination (normalized to body weight) did not differ. Moreover, voiding interval was significantly prolonged in aged rats during the active period. 2. In the presence of tetrodotoxin, pEC₅₀ of 5-HT were significantly lower in aged rats than in young rats (P < 0.01), but the maximal response to 5-HT was not altered in the aged bladder. Ketanserin inhibited 5-HT-induced contraction in both groups, while suppression by naftopidil was relatively limited, especially in aged rats. EFS induced neurogenic contraction in a frequency-dependent manner. Atropine-resistant contraction was not inhibited by naftopidil, but was potentiated by ketanserin.

Conclusions: Urination intervals were extended in aged rats, indicating that urination rhythm changed. In the senescent rat bladder, 5-HT induced detrusor contraction, but the effect of 5-HT and the naftopidil-sensitive contractile force were weaker than those in young rats. Additionally, 5-HT did not contribute to the increase in atropine-resistant EFS-induced contractions in aged rats.

Keywords: Aged rats; Ketanserin; Naftopidil; Serotonin; Urinary bladder; Voiding function.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adrenergic alpha-Antagonists / pharmacology
Animals
Atropine / pharmacology
Ketanserin / pharmacology
Male
Muscle Contraction / drug effects*
Naphthalenes / pharmacology*
Piperazines / pharmacology*
Rats
Rats, Inbred F344
Receptors, Serotonin, 5-HT2 / metabolism
Serotonin / pharmacology*
Serotonin Receptor Agonists / pharmacology
Tetrodotoxin
Urinary Bladder / drug effects*
Urinary Bladder / physiology*

Substances

Adrenergic alpha-Antagonists
Naphthalenes
Piperazines
Receptors, Serotonin, 5-HT2
Serotonin Receptor Agonists
Serotonin
Tetrodotoxin
Atropine
Ketanserin
naftopidil