Department of Oral Physiology, Showa University School of Dentistry, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo, 142-8555, Japan; Maxillofacial Oral Surgery, Showa University School of Dentistry, 2-1-1 Kitasenzoku, Ota-ku, Tokyo, 145-8515, Japan.
Department of Oral Physiology, Showa University School of Dentistry, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo, 142-8555, Japan.
Eur J Pharmacol. 2019 Oct 15;861:172601. doi: 10.1016/j.ejphar.2019.172601. Epub 2019 Aug 14.
Pharmacological agents that elevate dopamine and substance P concentrations have been suggested to prevent aspiration pneumonia and improve impaired swallowing processes. However, little is known about the effects of such agents on swallowing activities induced in motor nerves innervating the pharyngeal and laryngeal muscles. In this study, we examined the effects of imidapril, cilostazol, and amantadine, which are often prescribed for swallowing disorders, on swallowing motor activity. We recorded the efferent activities of the cervical vagal nerve, hypoglossal nerve, and phrenic nerve using arterially perfused rats aged between 21-35 postnatal days. The vagal nerve activity was used for evaluation of swallowing motor activity. When 1.25 ml of distilled water was injected into the oral cavity, or the superior laryngeal nerve was electrically stimulated, synchronized swallowing bursts were evoked in the vagal and hypoglossal nerves, while inspiratory discharges were inhibited in all the recorded nerves. Administration of imidapril (60 ng/ml) but not cilostazol (2.5 μg/ml) and amantadine (200 ng/ml) to the perfusate increased the mean peak amplitude of orally evoked swallowing bursts in the vagal nerve. Such increase in the peak amplitude by imidapril was antagonized by the administration of the NK receptor antagonist aprepitant (5 μg/ml) or the D receptor antagonist LE300 (2.5 μg/ml). In contrast, neither imidapril nor cilostazol caused a significant increase in swallowing bursts evoked by electrical stimulation of the superior laryngeal nerve. These results suggest that imidapril treatment may improve impaired swallowing by enhancing pharyngeal muscle activities via an increase in substance P and dopamine concentrations.
已有人提议使用提高多巴胺和 P 物质浓度的药物来预防吸入性肺炎和改善吞咽功能障碍。然而，人们对这些药物对支配咽和喉肌的运动神经诱导的吞咽活动的影响知之甚少。在这项研究中，我们检查了常用于吞咽障碍的依那普利、西洛他唑和金刚烷胺对吞咽运动活动的影响。我们使用经动脉灌注的出生后 21-35 天的大鼠记录颈迷走神经、舌下神经和膈神经的传出活动。迷走神经活动用于评估吞咽运动活动。当将 1.25ml 蒸馏水注入口腔或电刺激喉上神经时，迷走神经和舌下神经中会诱发同步的吞咽爆发，而所有记录的神经中的吸气放电均受到抑制。向灌流液中给予依那普利（60ng/ml）而非西洛他唑（2.5μg/ml）和金刚烷胺（200ng/ml）可增加迷走神经中口腔诱发的吞咽爆发的平均峰值幅度。依那普利引起的这种峰值幅度增加被 NK 受体拮抗剂 aprepitant（5μg/ml）或 D 受体拮抗剂 LE300（2.5μg/ml）的给药所拮抗。相比之下，依那普利和西洛他唑均未引起电刺激喉上神经诱发的吞咽爆发的显著增加。这些结果表明，依那普利治疗可能通过增加 P 物质和多巴胺浓度来改善咽肌活动，从而改善吞咽功能障碍。
