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Effects of L ‐arginine, mirabegron, and oxybutynin on the primary bladder afferent nerve activities synchronized with reflexic, rhythmic bladder contractions in the rat
Author(s) -
Aizawa Naoki,
Homma Yukio,
Igawa Yasuhiko
Publication year - 2015
Publication title -
neurourology and urodynamics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.918
H-Index - 90
eISSN - 1520-6777
pISSN - 0733-2467
DOI - 10.1002/nau.22571
Subject(s) - mirabegron , medicine , oxybutynin , overactive bladder , urology , stimulation , endocrinology , anesthesia , nocturia , pharmacology , urinary system , pathology , alternative medicine
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. Neurourol. Urodynam. 34:368–374, 2015 . © 2014 Wiley Periodicals, Inc.