Effects of nitric oxide inhibitors in mice with bladder outlet obstruction

Int Braz J Urol. 2017 Mar-Apr;43(2):356-366. doi: 10.1590/S1677-5538.IBJU.2015.0441.

Abstract

Purpose: To investigate the lower urinary tract changes in mice treated with L-NAME, a non-selective competitive inhibitor of nitric oxide synthase (NOS), or aminoguanidine, a competitive inhibitor of inducible nitric oxide synthase (iNOS), after 5 weeks of partial bladder outlet obstruction (BOO), in order to evaluate the role of constitutive and non-constitutive NOS in the pathogenesis of this experimental condition.

Materials and methods: C57BL6 male mice were partially obstructed and randomly allocated into 6 groups: Sham, Sham + L-NAME, Sham + aminoguanidine, BOO, BOO + L-NAME and BOO + aminoguanidine. After 5 weeks, bladder weight was obtained and cystometry and tissue bath contractile studies were performed.

Results: BOO animals showed increase of non-voiding contractions (NVC) and bladder capacity, and also less contractile response to Carbachol and Electric Field Stimulation. Inhibition of NOS isoforms improved bladder capacity and compliance in BOO animals. L-NAME caused more NVC, prevented bladder weight gain and leaded to augmented contractile responses at muscarinic and electric stimulation. Aminoguanidine diminished NVC, but did not avoid bladder weight gain in BOO animals and did not improve contractile responses.

Conclusion: It can be hypothesized that chronic inhibition of three NOS isoforms in BOO animals leaded to worsening of bladder function, while selective inhibition of iNOS did not improve responses, what suggests that, in BOO animals, alterations are related to constitutive NOS.

Keywords: NG-Nitroarginine Methyl Ester; Nitric Oxide; Urinary Bladder.

Publication types

  • Evaluation Study

MeSH terms

  • Animals
  • Enzyme Inhibitors / pharmacology*
  • Enzyme Inhibitors / therapeutic use
  • Guanidines / pharmacology*
  • Guanidines / therapeutic use
  • Lower Urinary Tract Symptoms / drug therapy*
  • Male
  • Mice, Inbred C57BL
  • Muscle Contraction / drug effects
  • NG-Nitroarginine Methyl Ester / pharmacology*
  • NG-Nitroarginine Methyl Ester / therapeutic use
  • Nitric Oxide / antagonists & inhibitors*
  • Nitric Oxide Synthase / antagonists & inhibitors*
  • Pressure
  • Random Allocation
  • Reproducibility of Results
  • Time Factors
  • Treatment Outcome
  • Urinary Bladder / drug effects
  • Urinary Bladder / physiopathology
  • Urinary Bladder Neck Obstruction / drug therapy*
  • Urinary Bladder Neck Obstruction / physiopathology
  • Urination / drug effects
  • Urination / physiology

Substances

  • Enzyme Inhibitors
  • Guanidines
  • Nitric Oxide
  • Nitric Oxide Synthase
  • pimagedine
  • NG-Nitroarginine Methyl Ester