Relationship Between α1-adrenergic Receptor Subtypes And The Contractile Function Of Instable Detrusor In Rats

Background and Objective: Detrusor instability (DI) secondary to the bladder outlet obstruction (BOO) is one of the most common micturational dysfunction in the field of urology. It can cause urinary frequency, urinary urgency, stress urinary incontinence, et al. It's hard to identify the pathogenesis of DI and the treatment for it is not effective enough until now. Although operation can take away some of the lower urinary tract symptoms (LUTS), other complications such as persistant irritative symptom also make patients distressed.Nowadays,α1A/D adrenergic receptor (AR) antagonist tamsulosin is always used to deal with the obstruction of voiding period and irritation of the storage period associated with patients who's suffered from benign prostatic hyperplasia (BPH). Such agents successfully removed the LUTS and improved the life quality of the patients. It is widely accepted that the obstructed symptoms can be treated by non-selectiveα1-AR antagonist by decreasing the tension of the bladder outlet, but it's commonly argued that whetherα1-AR and its subtypes can effect the detrusor and in which way they effect. To find the relationship betweenα1-AR and DI and identify the specificity of the receptor subtypes may help us to find other more effective therapies to BPH. The objective of this study is to investigate the effect ofα1D-AR andα1A-AR antagonists on unstable detrusor in rats secondary to BOO and the change of the detrusor contractility and autorythmicity through which we can approach the etiology of DI and the relationship between DI andα1-AR subtypes.Materials and Methods: Animal models of detrusor instability were made in female Wistar rats. After 6 weeks to enable the development of detrusor hypertrophy, filling cystometry was taken and the bladder smooth muscle was studied as isolated strips. The response produced byα1-AR agonist Phenylephrine and selectiveα1D-AR antagonist BMY 7378 andα1A-AR antagonist 5-MU were measured by means of the in vitro detrusor study. Frequency and amplitude of the DI and control muscle strips are taken to show the alteration of autorythmicity and contractility.Results and Discussion:①The cystometric results implied that the model of DI was stabilized established. 23 in 32 rats come up to the standard of DI. The incidence rate of DI was 71.9%.②The compliance and maximum cystometric capacity of rats is significantly increased after BOO.③Every group of isolate detrusor muscle strips can be induced to contracting at a very level of preload, and the detrusor autorythmicity and contractility increased evidently secondary to BOO.④The frequency and amplitude of the spontaneous contraction can be raised by PE in both DI and control group. The frequency and amplitude of the DI detrusor can be reduced by selectiveα1D-AR antagonist BMY 7378, which in control rats can be blocked by selectiveα1A-AR antagonist 5-MU.⑤contractile frequency and amplitude raised by PE in DI rats can be decreased byα1D-AR antagonist BMY 7378 which is able to decrease the frequency raised by PE in control group;α1A-AR antagonist 5-MU can decrease the frequency and amplitude raised by PE in control group evidently.Conclusion:Excitation ofα1-AR increases the frequency and amplitude of the detrusor. The modulation ofα1-AR on normal detrusor is taken byα1A-AR, but the change of function ofα1D-AR maybe plays a more important role than that ofα1A-AR in obstructive detrusor instability. These findings provide some evidence for us to support the theory in usingα1-AR antagonist to treat the LUTS secondary to BOO, chronic prostatitis and other diseases, and help us to make better use of superselectiveα1-AR subtype antagonists in the treatment of unstable bladder.