Umemura K, Kohno Y, Asai Y, Uematsu T, Nakashima M
Department of Pharmacology, Hamamatsu University School of Medicine, Japan.
Eur J Pharmacol. 1993 Aug 3;239(1-3):17-21. doi: 10.1016/0014-2999(93)90970-s.
We evaluated the effects of Ca2+ entry blockers, nilvadipine and flunarizine, on microcirculatory disorders of the inner ear and on blood flow in the inner ear of rats. Under sodium pentobarbital anesthesia, the middle ear was opened by a ventrolateral approach. A green light (wave length 540 nm) was applied to the cochlea or the vestibule to induce a hearing disturbance or equilibrium dysfunction as a result of inner ear microcirculatory disorders, while rose bengal solution was infused intravenously. In a hearing disturbance model, a compound cochlear nerve action potential was recorded by electrocochleography every minute after the beginning of illumination. The sound stimulus was an 8 kHz sine wave 100 dB normal hearing level. The action potential was calculated 128 times. The action potential disappeared about 12 min after the beginning of illumination. In another model of equilibrium dysfunction, the photoillumination was applied for 40 min under the infusion of rose bengal. The behavior of rats was observed in the swimming test and nystagmus was recorded 24 h after the completion of photoillumination. In a separate experiment, blood flow in the inner ear was measured with a laser Doppler flowmeter under sodium pentobarbital anesthesia. In this study, both nilvadipine and flunarizine prolonged the time required for complete suppression of the action potential, prevented equilibrium dysfunction in the swimming test and reduced the occurrence of nystagmus. Flunarizine significantly increased inner ear blood flow and nilvadipine failed to decrease blood flow in the inner ear, despite a reduced systemic blood pressure. In conclusion, Ca2+ entry blockers may prevent microcirculatory disorders of the inner ear in rats.
我们评估了钙离子通道阻滞剂尼伐地平与氟桂利嗪对大鼠内耳微循环障碍及内耳血流的影响。在戊巴比妥钠麻醉下，通过腹外侧入路打开中耳。将绿色光（波长540nm）照射于耳蜗或前庭，以诱发因内耳微循环障碍导致的听力障碍或平衡功能障碍，同时静脉输注孟加拉玫瑰红溶液。在听力障碍模型中，光照开始后每分钟用电耳蜗图记录复合蜗神经动作电位。声音刺激为8kHz正弦波，正常听力水平为100dB。动作电位计算128次。光照开始后约12分钟动作电位消失。在另一个平衡功能障碍模型中，在输注孟加拉玫瑰红的情况下进行40分钟光照。在游泳试验中观察大鼠行为，并在光照结束后24小时记录眼球震颤。在另一个单独实验中，在戊巴比妥钠麻醉下用激光多普勒血流仪测量内耳血流。在本研究中，尼伐地平和氟桂利嗪均延长了完全抑制动作电位所需的时间，预防了游泳试验中的平衡功能障碍，并减少了眼球震颤的发生。氟桂利嗪显著增加内耳血流，而尼伐地平尽管使全身血压降低，但未能降低内耳血流。总之，钙离子通道阻滞剂可能预防大鼠内耳的微循环障碍。
