Urodynamic analysis of age-related changes of alpha(1)-adrenoceptor responsiveness in female beagle dogs

Purpose: We have evaluated age-related changes of alpha(1)-adrenoceptor responsiveness in the lower urinary tract of female beagle dogs by urodynamic analyses. Materials and Methods: Six aged parous and 6 young nonparous female beagle dogs were studied. Mean ages (+/- standard error of the mean) of the 2 groups were 68.3 +/- 2.3 and 12.4 +/- 0.08 months. Before and after 4 administrations of alpha(1)-adrenoceptor agonist (midodrine hydrochloride 0.03, 0.1, 0.3 and 1.0 mg./kg. intravenously), cystometry, urethral pressure profilometry and external urethral sphincter electromyography were performed. Results: After 0.3 mg./kg. midodrine administration, mean bladder capacity in the aged dogs significantly decreased, compared with that in the young dogs (p < 0.05). After the minimum dose administration (0.03 mg./kg.), the urethral closing pressure in both groups increased significantly (p < 0.05) with no changes in bladder capacity or arterial blood pressure. The proximal urethral closing pressure in the aged dogs increased dose dependently. After administration of 1.0 mg./kg. drug it reached 257% of the initial values (p < 0.01), which was significantly greater than that in the young dogs (p < 0.05). Conclusions: These findings suggest that 1) age-related increase of alpha(1)-adrenoceptor responsiveness occurs in the bladder and in the proximal urethra. The former may be one of the etiologies of detrusor instability in the elderly. 2) A lower dose of midodrine hydrochloride may be useful for the treatment of stress incontinence, independent of age.