Effect of doxazosin on rat urinary bladder function after partial outlet obstruction

Area of Science:

• Urology
• Pharmacology
• Physiology

Background:

• Partial outlet obstruction causes bladder hypoxia, leading to hypertrophic and degenerative changes.
• Doxazosin (dox), an alpha-adrenergic antagonist, treats benign prostatic hyperplasia (BPH) by reducing urethral resistance.
• Dox may exert therapeutic effects via spinal or direct bladder actions, including vascular alpha-receptor inhibition.

Purpose of the Study:

• To investigate if dox pretreatment affects bladder blood flow and mitigates bladder dysfunction induced by partial outlet obstruction in rats.
• To explore potential non-prostatic mechanisms of dox action in bladder outlet obstruction.

Main Methods:

• Rats received oral dox (30 mg/kg) or vehicle for 4 weeks.
• Part 1: Blood flow was assessed using fluorescent microspheres.
• Part 2: Partial outlet obstruction was induced, and bladders were analyzed for weight and contractility in response to various stimuli (field stimulation, KCl, carbachol, ATP).

Main Results:

• Dox pretreatment significantly increased bladder blood flow in both control and obstructed rats.
• Dox treatment reduced the increase in bladder weight and preserved bladder contractility following partial outlet obstruction.
• Dox mitigated the reduction in contractile response to potassium chloride (KCl) induced by obstruction.

Conclusions:

• Doxazosin pretreatment enhances bladder blood flow and ameliorates bladder dysfunction associated with partial outlet obstruction.
• These findings suggest doxazosin has beneficial effects on the bladder independent of its action on prostate smooth muscle.
• Potential mechanisms include modulation of alpha-adrenergic systems affecting bladder vasculature, central nervous system micturition centers, spinal reflexes, or bladder/urethral receptors.