Combinational effects of muscarinic receptor inhibition and β3-adrenoceptor stimulation on neurogenic bladder dysfunction in rats with spinal cord injury.

Abstract

AIMS:

To investigate the effects of combined therapy with an anticholinergic agent and a β3-adrenoceptor agonist on bladder dysfunction and proliferation-related molecule expression in rats with spinal cord injury (SCI).

METHODS:

The spinal cord was transected at the level of T8-9 in female Sprague-Dawley rats, which were divided into four groups; A: Vehicle, B: 10 mg/kg/day of oxybutynin, C: 10 mg/kg/day of mirabegron, and D: combined administration of oxybutynin and mirabegron. Drugs were administered by oral gavage from 2 to 4 weeks after spinal cord transection. We evaluated urodynamic parameters and bladder tissue remodeling factors.

RESULTS:

Non-voiding contractions (NVCs) during the storage phase of cystometrograms tended to be decreased in all three treated groups with a significant reduction in group D versus A. Bladder compliance was improved, and intercontraction intervals, voided volume and bladder capacity were increased in group D. In all three treated groups (B-D), the expression of HIF1-α and TGF-β1 was decreased compared to group A. The expression of collagen-III and bFGF was decreased in groups B and D. The total bladder elastin level was increased in group D.

CONCLUSIONS:

The combination therapy of an anticholinergic agent and a β3-adrenoceptor agonist elevated the bladder elastin level, reduced NVCs, and increased bladder compliance more effectively than the monotherapy in SCI rats. Thus, the combination therapy could be effective for the treatment of neurogenic bladder dysfunction including bladder remodeling. Neurourol. Urodynam. 36:1039-1045, 2017. © 2016 Wiley Periodicals, Inc.

• Authors: Naoki Wada, Takahiro Shimizu, Shun Takai, Nobutaka Shimizu, Pradeep Tyagi, Hidehiro Kakizaki, Naoki Yoshimura
• Journal: Neurourology and urodynamics (Neurourol Urodyn) Vol. 36 Issue 4 Pg. 1039-1045 (04 2017) ISSN: 1520-6777 [Electronic] United States
• PMID: 27367752 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S., Research Support, N.I.H., Extramural)
• Copyright: © 2016 Wiley Periodicals, Inc.

Chemical References

• Acetanilides
• Adrenergic beta-3 Receptor Agonists
• Mandelic Acids
• Muscarinic Antagonists
• Thiazoles
• Urological Agents
• oxybutynin
• mirabegron

Topics

• Acetanilides (pharmacology, therapeutic use)
• Adrenergic beta-3 Receptor Agonists (pharmacology, therapeutic use)
• Animals
• Disease Models, Animal
• Drug Therapy, Combination
• Female
• Mandelic Acids (pharmacology, therapeutic use)
• Muscarinic Antagonists (pharmacology, therapeutic use)
• Rats
• Rats, Sprague-Dawley
• Spinal Cord Injuries (complications)
• Thiazoles (pharmacology, therapeutic use)
• Urinary Bladder (drug effects, physiopathology)
• Urinary Bladder, Neurogenic (drug therapy, etiology, physiopathology)
• Urination (drug effects)
• Urodynamics (drug effects)
• Urological Agents (pharmacology, therapeutic use)