Nonselective blocking of the sympathetic nervous system decreases detrusor overactivity in spontaneously hypertensive rats

Int J Mol Sci. 2012;13(4):5048-5059. doi: 10.3390/ijms13045048. Epub 2012 Apr 23.

Abstract

The involuntary dual control systems of the autonomic nervous system (ANS) in the bladder of awake spontaneously hypertensive rats (SHRs) were investigated through simultaneous registrations of intravesical and intraabdominal pressures to observe detrusor overactivity (DO) objectively as a core symptom of an overactive bladder. SHRs (n = 6) showed the features of overactive bladder syndrome during urodynamic study, especially DO during the filling phase. After injection of the nonselective sympathetic blocking agent labetalol, DO disappeared in 3 of 6 SHRs (50%). DO frequency decreased from 0.98 ± 0.22 min(-1) to 0.28 ± 0.19 min(-1) (p < 0.01), and DO pressure decreased from 3.82 ± 0.57 cm H(2)O to 1.90 ± 0.86 cm H(2)O (p < 0.05). This suggests that the DO originating from the overactive parasympathetic nervous system is attenuated by the nonselective blocking of the sympathetic nervous system. The detailed mechanism behind this result is still not known, but parasympathetic overactivity seems to require overactive sympathetic nervous system activity in a kind of balance between these two systems. These findings are consistent with recent clinical findings suggesting that patients with idiopathic overactive bladder may have ANS dysfunction, particularly a sympathetic dysfunction. The search for newer and better drugs than the current anticholinergic drugs as the mainstay for overactive bladder will be fueled by our research on these sympathetic mechanisms. Further studies of this principle are required.

Keywords: autonomic nervous system; detrusor overactivity; labetalol.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antihypertensive Agents / pharmacology*
  • Autonomic Nervous System / drug effects*
  • Autonomic Nervous System / physiology
  • Blood Pressure / drug effects
  • Cholinergic Antagonists / pharmacology
  • Female
  • Labetalol / pharmacology*
  • Male
  • Rats
  • Rats, Inbred SHR
  • Rats, Wistar
  • Sympathetic Nervous System / drug effects*
  • Sympathetic Nervous System / physiology
  • Urinary Bladder, Overactive / drug therapy*

Substances

  • Antihypertensive Agents
  • Cholinergic Antagonists
  • Labetalol