MP1-06 IN VIVO AND IN VITRO BLADDER DYSFUNCTION IN AGED MICE AND ITS SEX DIFFERENCES

Abstract

INTRODUCTION AND OBJECTIVES: Precise pathophysiology of age-related bladder dysfunction has not been fully clarified yet. In the present study, we aimed to investigate age-related changes in the bladder function of the mouse by using precise frequency volume (FV) measurements, in vitro contractile studies and histological examination of detrusor strips. Gender differences in the age-related changes were also determined. METHODS: C57/BL6 male and female mice were divided into two groups: control (CONT: 12 months-old; n1⁄48 of each sex) and aged (AGED: 27-30 months-old; male: n1⁄46, female: n1⁄47). After FV measurements, in vitro organ bath studies using detrusor strips were carried out to evaluate their contractile responses to high K+ (KCl: 62 mM), carbachol (CCh: 10-3-10-8 M), and to electrical field stimulation (EFS; 2-20 Hz) in the absence and presence of atropine (10-6 M), a,b-methylene ATP (M-ATP: 10-5 M x 5 times). In separate detrusor strips, the muscle/collagen ratio was evaluated by using Masson-trichrome staining. RESULTS: In the FV measurement, there were no significant differences in mean voided volume per micturition between CONT and AGED in either sex, although AGED of both sexes had larger total voided volume per day. Female AGED showed a decreased mean uroflow rate. The contractile responses to high K+ were weaker in AGED of both sexes (Fig.). In addition, those to CCh and EFS were decreased with aging in both sexes, but when standardized by the high K+-induced contraction, the contractile responses to CCh were stronger in AGED of both sexes (Fig.), and those to EFS were stronger only in female AGED. Moreover, AGED of both sexes showed a decreased atropine-sensitive component and an increased M-ATP-sensitive component of the EFS-induced contractions. The muscle/collagen ratio in the muscle layer did not change significantly with aging in either gender. CONCLUSIONS: The current in vitro functional studies with analysis of muscle/collagen ratio indicate the intrinsic contractile property of detrusor smooth muscle in both sexes is potentially impaired with aging. The findings that the contractile responses standardized by the high K+ -induced contraction to CCh and EFS were increased in the aged bladder, suggest a compensatory mechanism for the myogenic impairment. This compensatory mechanism may make the impairment of in vivo bladder function minimal. Source of Funding: none