Therapeutic effects of silodosin and urapidil on underactive bladder associated with diabetic cystopathy.

Abstract

Pharmacological treatment options for underactive bladder (UAB) syndrome are limited. Urapidil is the only alpha1 -adrenoceptor (AR) antagonist that can be used for urinary disorders in women in some countries. However, no studies have directly verified the effects of alpha1 -AR antagonists on the female urethra and UAB-like dysfunctions. We investigated the effects of silodosin (alpha1A -AR antagonist) and urapidil (nonselective alpha1 -AR antagonist) on the voiding function in female rats with diabetes mellitus (DM). Changes in intraurethral pressure (IUP) induced by midodrine (alpha1 -AR agonist) and mean blood pressure (MBP) were continuously measured in normal female rats to verify the pharmacological profiles of the drugs. To establish a DM model, rats were administered streptozotocin (STZ; 50 mg/kg, intravenous). Eight weeks after STZ administration, drugs were subcutaneously delivered through an osmotic pump. Four weeks after drug administration, emptied bladder blood flow (BBF), intravesical pressure, and the micturition volume were measured. Both silodosin and urapidil inhibited the midodrine-induced increase in IUP and decreased MBP in a dose-dependent manner. Silodosin had a more substantial effect on the lower urinary tract than on MBP. Twelve weeks after STZ administration, DM rats exhibited UAB-like dysfunction (increased bladder capacity/bladder weight and residual volume and decreased bladder voided efficiency) and decreased BBF. Both drug treatments controlled this dysfunction. Alpha1 -AR antagonists induced dose-dependent urethral relaxation in female rats. These drugs ameliorated UAB-like dysfunction in STZ-induced DM rats. In addition, alpha1A -AR antagonists such as silodosin, which have limited effects on blood pressure, appear to be useful for treating UAB.