Differential vulnerabilities of urethral afferents in diabetes and discovery of a novel urethra-to-urethra reflex.
Differential vulnerabilities of urethral afferents in diabetes and discovery of a novel urethra-to-urethra reflex.
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DOI：
10.1152/ajprenal.00281.2009
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发表时间：
2010
期刊：
影响因子：
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通讯作者：
Zhongguang Yang;P. C. Dolber;M. Fraser
中科院分区：
文献类型：
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作者：
Zhongguang Yang;P. C. Dolber;M. Fraser
尿道反射是排尿的重要调节器，并且尿道传入神经元功能的损伤可能破坏协调的膀胱和尿道活动，从而导致下尿路疾病中的排尿功能障碍。通过尿道内刺激溶液灌注的化学刺激来确定糖尿病（DM）患者尿道传入神经元功能是否改变。在注射链脲佐菌素以诱导DM或单独媒介物后10周，研究Sprague-Dawley大鼠。递增剂量的辣椒素（0.1-30 μ M）或乙酸（0.01-1%; AA）经尿道内灌注，同时记录等容膀胱活动、尿道灌注压和尿道外括约肌肌电图（EUS-EMG）。一些大鼠还接受了α-银环蛇毒素、六甲铵或阴部神经感觉分支双侧横断（PudSNx）处理。尿道内辣椒素抑制膀胱收缩在六个七个对照组大鼠，但没有在任何六个糖尿病大鼠。在辣椒素诱导的膀胱抑制的6只对照大鼠中的5只中观察到尿道内压的低频振荡（LFOs）。相比之下，尿道内AA抑制膀胱收缩和增强紧张性EUS-EMG活动在六个控制和五个DM大鼠。AA诱导膀胱抑制的6只对照大鼠中有4只发生LFO，5只DM大鼠中有3只发生LFO。化学诱导的膀胱抑制和LFO不能通过α-银环蛇毒素预防，但可以通过PudSNx和六甲双铵消除。最后，LFO之后是阶段性EUS活动。这些发现表明，DM影响尿道传入神经元的差异，损害那些表达TRPV 1受体。尿道平滑肌LFO是神经源性介导的，并诱导EUS活动，揭示了迄今未描述的反射途径的存在：平滑肌尿道-尿道反射。
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.