Differential vulnerabilities of urethral afferents in diabetes and discovery of a novel urethra-to-urethra reflex

Zhongguang Yang, Paul C. Dolber, Matthew O. Fraser

Research output: Contribution to journalArticle

16 Citations (Scopus)

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 μM) 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 α-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 α-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.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Renal Physiology
Volume298
Issue number1
DOIs
StatePublished - Jan 2010
Externally publishedYes

Fingerprint

Urethra
Reflex
Urinary Bladder
Diabetes Mellitus
Capsaicin
Bungarotoxins
Hexamethonium
Perfusion
Chemical Stimulation
Pudendal Nerve
Pressure
Afferent Neurons
Striated Muscle
Urination
Irritants
Electromyography
Streptozocin
Urinary Tract
Acetic Acid
Smooth Muscle

Keywords

  • Acetic acid
  • Bladder
  • Capsaicin
  • Diabetes mellitus
  • External urethral sphincter
  • Urethra

ASJC Scopus subject areas

  • Physiology
  • Urology
  • Medicine(all)

Cite this

Differential vulnerabilities of urethral afferents in diabetes and discovery of a novel urethra-to-urethra reflex. / Yang, Zhongguang; Dolber, Paul C.; Fraser, Matthew O.

In: American Journal of Physiology - Renal Physiology, Vol. 298, No. 1, 01.2010.

Research output: Contribution to journalArticle

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