Karl-Erik Andersson led the peer-review process as the Associate Editor responsible for the paper.
Effects of L-arginine, mirabegron, and oxybutynin on the primary bladder afferent nerve activities synchronized with reflexic, rhythmic bladder contractions in the rat
Article first published online: 14 FEB 2014
© 2014 Wiley Periodicals, Inc.
Neurourology and Urodynamics
Volume 34, Issue 4, pages 368–374, April 2015
How to Cite
Aizawa, N., Homma, Y. and Igawa, Y. (2015), 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., 34: 368–374. doi: 10.1002/nau.22571
Conflict of interest: This study was supported by the research grant from Astellas Pharma Inc. (Tokyo, Japan).
- Issue published online: 10 APR 2015
- Article first published online: 14 FEB 2014
- Manuscript Accepted: 20 JAN 2014
- Manuscript Received: 31 OCT 2013
- Grant-in-Aid for Scientific Research (YI and NA). Grant Numbers: 40159588, 80595257
- Astellas Pharma Inc. (Tokyo, Japan)
- nitric oxide;
- Sprague-Dawley rats;
- urinary bladder
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.
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.
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.
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. Neurourol. Urodynam. 34:368–374, 2015. © 2014 Wiley Periodicals, Inc.