Functional roles of bladder α1-adrenoceptors in the activation of single-unit primary bladder afferent activity in rats.
To clarify the involvement of bladder α1-adrenoceptors (α1-ARs) in afferent pathways by investigating the effects of silodosin and BMY7378, selective α1A- or α1D-AR antagonists, respectively, on single-unit afferent nerve fibre activity (SAA) of the primary bladder afferent nerves and their relationship with bladder microcontractions in rats.



A total of 63 female Sprague-Dawley rats were anaesthetized with urethane. The SAA of Aδ and C fibres generated from the left L6 dorsal roots was determined using electrical stimulation of the left pelvic nerve and bladder distension. After measuring baseline SAA during constant filling cystometry, the procedure was repeated with i.v. (0.3-30 μg/kg) or intravesical (10 μm) administration of each antagonist. In separate rats, the bladder was filled with saline until the intravesical pressure reached 30 cmH2 O, and was kept under isovolumetric conditions, then the recording was performed with i.v.-administered vehicle and silodosin (0.3 μg/kg).



A total of Aδ fibres and 33 C fibres were isolated from 63 rats. The SAA of Aδ fibres, but not C fibres, were dose-dependently decreased after both i.v. and intravesical administrations of each of the antagonists. In the experiments under bladder isovolumetric conditions, silodosin administration significantly decreased the SAA of Aδ fibres, but not C fibres, compared with vehicle administration. There were no significant effects on either the mean basal bladder pressure or microcontractions.



The present study suggests that both α1A- or α1D-ARs in the rat bladder are involved in the activation of the bladder mechanosensory Aδ fibres during bladder filling, and that this activation may not be related to bladder microcontractions.
Department of Continence Medicine, The University of Tokyo Graduate School of Medicine, Tokyo, Japan.
Naoki
N
Aizawa
Department of Continence Medicine, The University of Tokyo Graduate School of Medicine, Tokyo, Japan.
Rino
R
Sugiyama
Department of Continence Medicine, The University of Tokyo Graduate School of Medicine, Tokyo, Japan.
Koji
K
Ichihara
Department of Urology, The University of Tokyo Graduate School of Medicine, Tokyo, Japan.
Tetsuya
T
Fujimura
Department of Urology, The University of Tokyo Graduate School of Medicine, Tokyo, Japan.
Hiroshi
H
Fukuhara
Department of Urology, The University of Tokyo Graduate School of Medicine, Tokyo, Japan.
Yukio
Y
Homma
Department of Continence Medicine, The University of Tokyo Graduate School of Medicine, Tokyo, Japan.
Yasuhiko
Y
Igawa
D058665:Adrenergic beta-1 Receptor Agonists / Q000494:pharmacology; D058671:Adrenergic beta-1 Receptor Antagonists / Q000494:pharmacology; D000818:Animals; D005260:Female; D009119:Muscle Contraction / Q000187:drug effects; D036421:Nerve Fibers, Unmyelinated / Q000187:drug effects; D009475:Neurons, Afferent / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018342:Receptors, Adrenergic, beta-1 / Q000502:physiology*; D001743:Urinary Bladder / Q000187:drug effects / Q000294:innervation / Q000502:physiology*
D058665:Adrenergic beta-1 Receptor Agonists; D058671:Adrenergic beta-1 Receptor Antagonists; D018342:Receptors, Adrenergic, beta-1
Sprague-Dawley rats; adrenergic α-1 receptor antagonists; afferent; urinary bladder