Effects of L-arginine, mirabegron, and oxybutynin on the primary bladder afferent nerve activities synchronized with reflexic, rhythmic bladder contractions in the rat

Neurourol Urodyn. 2015 Apr;34(4):368-74. doi: 10.1002/nau.22571. Epub 2014 Feb 14.

Abstract

Aims: We measured single-unit mechanosensitive afferent activities (SAAs) during reflexic, rhythmic bladder contractions (RBCs), and examined whether L-arginine, an NO substrate, and mirabegron, a β3-adrenoceptor agonist, and oxybutynin, an antimuscarinic agent, can affect the SAAs in such condition.

Methods: Twenty-nine female Sprague-Dawley rats were anesthetized. SAA was identified by electro-stimulation of the left pelvic nerve and by bladder distension, and was divided into Aδ- or C-fibers by conduction velocity. To produce the RBCs, right L6 dorsal roots were kept intact. Under an isovolumetric condition, vehicle and L-arginine (300 mg/kg) or mirabegron (1 mg/kg) or oxybutynin (1 mg/kg) were administered intravenously.

Results: All of the Aδ- (n = 26) and C-fibers (n = 29) capable of responding to bladder distention were also responsive to bladder contractions during RBCs. The amplitude and duration of RBCs significantly decreased after mirabegron- and oxybutynin-administrations, but not after L-arginine-administration. The interval of RBC was significantly elongated after L-arginine- and mirabegron-administrations. Regarding the SAAs, the peaks of firing rate (FR) during RBCs and FR during the non-contractile phase were decreased after L-arginine-administration, which were more remarkable for Aδ-fibers than C-fibers. Similar results were observed after mirabegron-administration only for Aδ-fibers. After oxybutynin-administration, the peak of FR of both fiber-SAAs significantly decreased, but the change was not significant when the value was normalized by the amplitude of RBCs.

Conclusions: The present results indicate that mechanosensitive Aδ- and C-fibers were also responsive to bladder contractions, and that NO production and β3-adrenoceptor stimulation can inhibit SAAs mainly of Aδ-fibers synchronized with RBCs.

Keywords: Sprague-Dawley rats; afferent; nitric oxide; urinary bladder; β3-adrenoceptor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetanilides / pharmacology*
  • Adrenergic beta-3 Receptor Agonists / pharmacology*
  • Animals
  • Arginine / pharmacology*
  • Electric Stimulation
  • Female
  • Mandelic Acids / pharmacology*
  • Mechanotransduction, Cellular / drug effects
  • Muscarinic Antagonists / pharmacology*
  • Muscle Contraction / drug effects*
  • Muscle, Smooth / drug effects*
  • Muscle, Smooth / innervation
  • Muscle, Smooth / metabolism
  • Nerve Fibers, Myelinated / drug effects
  • Nerve Fibers, Unmyelinated / drug effects
  • Neurons, Afferent / drug effects*
  • Nitric Oxide / metabolism
  • Periodicity*
  • Pressure
  • Rats, Sprague-Dawley
  • Reflex / drug effects*
  • Thiazoles / pharmacology*
  • Time Factors
  • Urinary Bladder / drug effects*
  • Urinary Bladder / innervation
  • Urinary Bladder / metabolism

Substances

  • Acetanilides
  • Adrenergic beta-3 Receptor Agonists
  • Mandelic Acids
  • Muscarinic Antagonists
  • Thiazoles
  • Nitric Oxide
  • Arginine
  • oxybutynin
  • mirabegron