Mechanisms of action for α1-adrenoceptor blockers in storage symptoms with new insights into the micturition reflex

Life Sci. 2017 Dec 15:191:90-96. doi: 10.1016/j.lfs.2017.10.015. Epub 2017 Oct 12.

Abstract

Elderly patients suffering from lower urinary tract symptoms with benign prostatic hyperplasia (BPH) are widely prescribed α1-adrenoceptor blockers (α1-blockers) to improve voiding and storage symptoms. The mechanism of action for improvements in voiding symptoms is well understood; tonus of the urethra and prostate are decreased and urinary flow rate is increased by α1-blockers. However, the mechanisms underlying storage symptoms have remained unclear, although detrusor hyperactivity has been identified as a significant factor. Previous investigations have yielded informative results, such as amelioration of reduced blood flow and afferent C-fiber activation, and the importance of the urothelium. Recently, the fascinating role of α1A- and α1D-adrenoceptor subtypes have been investigated for bladder function. Furthermore, the scope of this pathology covers both the bladder and that part of the central nervous system related to the micturition reflex. This review describes the beneficial effects of α1-blockers on storage symptoms and the pathogenesis of storage symptoms related to BPH, discusses the mechanisms of action for α1-blockers with reference to results from cystometry to suggest improvements in management that suppress detrusor hyperactivity, and examines the potential influence of α1A- and α1D-adrenoceptor subtypes on bladder activity.

Keywords: Benign prostatic hyperplasia; Micturition reflex; Partial bladder outlet obstruction; Storage symptom; α(1)-Adrenoceptor blocker.

Publication types

  • Review

MeSH terms

  • Adrenergic alpha-1 Receptor Antagonists / pharmacology
  • Adrenergic alpha-1 Receptor Antagonists / therapeutic use*
  • Animals
  • Brain / drug effects
  • Brain / metabolism
  • Humans
  • Lower Urinary Tract Symptoms / complications*
  • Lower Urinary Tract Symptoms / drug therapy*
  • Lower Urinary Tract Symptoms / metabolism
  • Male
  • Prostatic Hyperplasia / complications*
  • Receptors, Adrenergic, alpha-1 / metabolism*
  • Spinal Cord / drug effects
  • Spinal Cord / metabolism
  • Urinary Bladder / drug effects
  • Urinary Bladder / metabolism
  • Urination / drug effects*

Substances

  • Adrenergic alpha-1 Receptor Antagonists
  • Receptors, Adrenergic, alpha-1