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

Neurourology and urodynamics

PubMedID: 24532414

Aizawa N, Homma Y, Igawa Y. 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. 2014;.
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 ß3-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 Ad- 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 Ad- (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 Ad-fibers than C-fibers. Similar results were observed after mirabegron-administration only for Ad-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 Ad- and C-fibers were also responsive to bladder contractions, and that NO production and ß3-adrenoceptor stimulation can inhibit SAAs mainly of Ad-fibers synchronized with RBCs. Neurourol. Urodynam. © 2014 Wiley Periodicals, Inc.