Takeya Kitta1,2, Satoru Yoshikawa1, Naoki Kawamorita1, William C de Groat3, Katsuya Nonomura2, Naoki Yoshimura1,3. 1. Department of Urology, University of Pittsburgh, Pittsburgh, Pennsylvania. 2. Department of Renal and Genitourinary Surgery, Graduate School of Medicine, Hokkaido University, Sapporo, Japan. 3. Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, Pennsylvania.
Abstract
AIMS: Stress urinary incontinence (SUI) is common in post-menopausal women. The present study therefore examined how aging and estrogen deficiency induced by ovariectomy (OVX) affect the urethral continence mechanism that prevents sneeze-induced SUI in rats. METHODS: Young (3 months old) and middle-aged (12 months old) female rats underwent bilateral OVX or sham operation. Urethral activity was measured by the amplitude of urethral responses during sneezing (A-URS) and urethral baseline pressure (UBP). Apoptotic changes in urethral tissue sections were examined by the TUNEL method. RESULTS: In middle-aged rats, UBP, but not A-URS, was significantly decreased compared to young rats. In 3-week OVX rats, A-URS was significantly decreased compared to sham rats in both young and middle-aged groups, and the OVX-induced reduction in A-URS was more pronounced in middle-aged rats. Neither young 3-week OVX nor sham rats leaked during sneezing; however, SUI occurred in 2/8 middle-aged rats with 3-week OVX, and after 6 weeks of OVX, SUI was observed in 5/8 young rats and 6/8 middle-aged rats. In middle-aged rats, TUNEL positive cells were significantly increased in urethral striated muscles whereas, after OVX, the increased number of positive cells was also found in the mucosa. CONCLUSIONS: These results indicate that aging is more likely to impair baseline urethral function than striated muscle-mediated reflex activity although apoptotic changes are found in urethral striated muscle. Estrogen deficiency additionally impairs the striated muscle-mediated continence reflex. Thus, aging and estrogen deficiency differently and additively affect baseline urethral function and neurally-evoked, striated muscle-mediated urethral continence mechanisms to induce SUI.
AIMS: Stress urinary incontinence (SUI) is common in post-menopausal women. The present study therefore examined how aging and estrogen deficiency induced by ovariectomy (OVX) affect the urethral continence mechanism that prevents sneeze-induced SUI in rats. METHODS: Young (3 months old) and middle-aged (12 months old) female rats underwent bilateral OVX or sham operation. Urethral activity was measured by the amplitude of urethral responses during sneezing (A-URS) and urethral baseline pressure (UBP). Apoptotic changes in urethral tissue sections were examined by the TUNEL method. RESULTS: In middle-aged rats, UBP, but not A-URS, was significantly decreased compared to young rats. In 3-week OVX rats, A-URS was significantly decreased compared to sham rats in both young and middle-aged groups, and the OVX-induced reduction in A-URS was more pronounced in middle-aged rats. Neither young 3-week OVX nor sham rats leaked during sneezing; however, SUI occurred in 2/8 middle-aged rats with 3-week OVX, and after 6 weeks of OVX, SUI was observed in 5/8 young rats and 6/8 middle-aged rats. In middle-aged rats, TUNEL positive cells were significantly increased in urethral striated muscles whereas, after OVX, the increased number of positive cells was also found in the mucosa. CONCLUSIONS: These results indicate that aging is more likely to impair baseline urethral function than striated muscle-mediated reflex activity although apoptotic changes are found in urethral striated muscle. Estrogen deficiency additionally impairs the striated muscle-mediated continence reflex. Thus, aging and estrogen deficiency differently and additively affect baseline urethral function and neurally-evoked, striated muscle-mediated urethral continence mechanisms to induce SUI.