Function of the lower urinary tract in mice lacking α1d-adrenoceptor

Purpose: alpha(1)-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 alpha(1d)-AR using frequency/volume analysis and filling cystometry. Materials and Methods: A total of 10, 12-week-old female alpha(1d)-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 alpha(1)-AR subtype mRNA in the bladder of mice in each group was quantified using real-time polymerase chain reaction. Results: Mean daily voiding frequency +/- SD in alpha(1d)-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 alpha(1d)-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 alpha(1d)-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 alpha(1a), alpha(1b) and alpha(1d)-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, alpha(1d)-AR transcript was not detectable in alpha(1d)-KO mice but alpha(1a) and alpha(1b)-AR expression was similar to that in WT mice. Conclusions: The results demonstrate that the alpha(1d)-AR subtype has an important role in regulating bladder function. They theoretically support a clinical finding that alpha(1)-blockers with significant affinity for alpha(1d)-AR are effective for treating storage symptoms associated with benign prostatic obstruction.