FUNCTION OF THE LOWER URINARY TRACT IN MICE LACKING α 1d -ADRENOCEPTOR

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Abstract
α1-Adrenoceptor (AR) blockers are known to relieve not only voiding symptoms, but also storage symptoms in elderly men. We investigated lower urinary tract function in mice lacking α1d-AR using frequency/volume analysis and filling cystometry. A total of 10, 12-week-old female α1d-knockout (KO) mice and 10 age matched female wild-type (WT) mice were studied. Each mouse was placed in a metabolic cage connected to a digital scale and personal computer. Under a 12/12-hour dark/light photocycle voiding frequency and volume were recorded for 48 hours. After frequency/volume analysis filling cystometry was performed with the mice awake and without restraint. The expression of α1-AR subtype mRNA in the bladder of mice in each group was quantified using real-time polymerase chain reaction. Mean daily voiding frequency ± SD in α1d-KO mice was 9.0 ± 2.1, significantly lower than 15.9 ± 5.2 in WT mice (p = 0.0048). Mean volume per void in α1d-KO mice was significantly larger than in WT mice (0.24 ± 0.02 vs 0.16 ± 0.03 ml, p = 0.0096). Similarly cystometric analysis demonstrated larger bladder capacity (140%, p = 0.0008) and voided volume (146%, p = 0.0048) in α1d-KO mice compared with those in WT mice. No significant difference in maximum pressure at void was observed between the 2 groups. In WT mice the amount of α1a, α1b and α1d-AR subtype mRNA in the bladder was 5.2 ± 0.7, 1.0 ± 0.1 and 6.3 ± 0.7 gene copies per ng total RNA, respectively. In contrast, α1d-AR transcript was not detectable in α1d-KO mice but α1a and α1b-AR expression was similar to that in WT mice. The results demonstrate that the α1d-AR subtype has an important role in regulating bladder function. They theoretically support a clinical finding that α1-blockers with significant affinity for α1d-AR are effective for treating storage symptoms associated with benign prostatic obstruction.