Differential vulnerabilities of urethral afferents in diabetes and discovery of
a novel urethra-to-urethra reflex.
Authors Yang Z, Dolber PC, Fraser MO
Submitted By Matthew Fraser on 3/31/2010
Status Published
Journal American journal of physiology. Renal physiology
Year 2010
Date Published 1/1/2010
Volume : Pages 298 : F118 - F124
PubMed Reference 19864303
Abstract Urethral reflexes are important regulators of micturition, and impairment of
urethral afferent neuronal function may disrupt coordinated bladder and urethral
activity, thereby contributing to voiding dysfunction in lower urinary tract
disorders. Chemical stimulation by intraurethral irritant solution perfusion was
used to determine whether urethral afferent neuronal function is altered in
diabetes mellitus (DM). Sprague-Dawley rats were studied 10 wk after
streptozotocin injection to induce DM or vehicle alone. Escalating doses of
capsaicin (0.1-30 microM) or acetic acid (0.01-1%; AA) were perfused
intraurethrally while recording isovolumetric bladder activity, urethral
perfusion pressure, and electromyography of the external urethral sphincter
(EUS-EMG). Some rats were additionally treated with alpha-bungarotoxin,
hexamethonium, or bilateral transection of the sensory branches of the pudendal
nerves (PudSNx). Intraurethral capsaicin inhibited bladder contractions in six
out of seven control rats but not in any of six DM rats. Low-frequency
oscillations (LFOs) of intraurethral pressure were observed in five out of six
control rats with capsaicin-induced bladder inhibition. In contrast,
intraurethral AA inhibited bladder contractions and enhanced tonic EUS-EMG
activity in six out of six control and five out of six DM rats. LFOs occurred in
four out of six control and three of five DM rats with AA-induced bladder
inhibition. Chemically induced bladder inhibition and LFOs were not prevented by
alpha-bungarotoxin but were eliminated by PudSNx and hexamethonium. Finally,
LFOs were followed by phasic EUS activity. These findings show that DM affects
urethral afferent neurons differentially, compromising those expressing TRPV1
receptors. Urethral smooth muscle LFOs are neurogenically mediated and induce
EUS activity, revealing the existence of a hitherto undescribed reflex pathway:
a smooth-to-striated muscle urethra-to-urethra reflex.


Investigators with authorship
NameInstitution
Matthew FraserDuke University Medical Center

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