Young rats exhibit an age- and sex-dependent bladder response to alpha-antagonists but not beta-agonists

Previous studies have suggested that the onset of alpha- (α) and beta- (β) adrenergic receptor activity is delayed in young animals. The use of alpha1- (α1-) antagonists for dysfunctional voiding, and beta3- (β3-) agonists for overactive bladder in younger children may not be indicated if maturation is required before bladder and urethral adrenergic receptors are active.

To determine the sex- and age-dependent responses of the bladder and external urethral sphincter (EUS) to α- and β-adrenergic agents in neonatal and young adult rats.

A total of 72 naïve Sprague-Dawley rats (36 female, 36 male) and 15 bladder-reduced (BR) female Sprague-Dawley rats underwent cystometry and EUS electromyography at 3, 6, and 9 weeks of life. Following administration of WAY 100,635 (0.3 mg/kg, serotonergic receptor antagonist), the non-selective α-agonist phenylephrine (0.3 mg/kg), α-antagonist phentolamine (1-3 mg/kg), β-agonist isoprenaline (3 mg/kg) and β-antagonist propranolol (3 mg/kg) were delivered intravenously. The maximum intravesical pressure (IVP), pressure threshold (PT), intermicturition interval (IMI), contraction duration (CD), burst amplitude and burst frequency were compared after each drug.

The α-antagonist phentolamine lowered the IVP in 9-week-old males without lowering the PT. In contrast, the β-agonist isoprenaline lowered the IVP in both males and females of all ages, also without affecting the PT. Isoprenaline was also effective at shortening the CD in females, suggesting more effective bladder emptying. The α-agonist phenylephrine increased the IVP in 3-week-old and 6-week-old females and 3-week-old males, but this effect was blocked by pretreatment with phentolamine. The β-antagonist propranolol increased the PT in both males and females, and shortened the IMI in females, which was consistent with retention. Phenylephrine increased the burst duration in 9-week-old naïve females, while isoprenaline increased the burst amplitude and duration in 9-week-old BR females.

In the neonatal rat, both α- and β-adrenergic receptors actively regulate bladder function by 3 weeks of life, but the desired effect of decreasing IVP by α-antagonists was delayed until 9 weeks in male rats. In contrast, β-agonists were effective at decreasing IVP in both male and female rats of all ages, which suggests that they are better agents for enhancing bladder emptying in female and young male rats.