Dehydration effects of a V2 antagonist on endolymphatic hydrops in guinea pigs
Dehydration effects of a V2 antagonist on endolymphatic hydrops in guinea pigs
复制标题
DOI：
10.1016/j.heares.2015.12.017
复制
发表时间：
2016-02-01
期刊：
影响因子：
2.8
通讯作者：
Yamasoba, Tatsuya
中科院分区：
文献类型：
--
作者：
Egami, Naoya;Kakigi, Akinobu;Yamasoba, Tatsuya
我们研究了 2 型加压素受体拮抗剂（OPC-41061；托伐普坦）对豚鼠实验诱导的内淋巴积水 (EH) 的影响。在第一个系列中，所有动物左耳的内淋巴囊（ES）均被电灼。手术后 4 周，将动物分为四组：三个全身应用组（盐水、OPC 10 和 100 mg/kg）和局部圆窗（RW）OPC 1 mg/身体应用组。我们检查了颞骨的组织病理学，并评估了耳蜗和球囊内淋巴空间的体积变化。在第二个系列中，我们研究了 OPC 的全身和局部应用对血浆加压素 (p-VP) 浓度和血浆渗透压 (p-OSM) 的影响。在第一个系列中，我们发现 OPC 10 mg/kg 全身给药组和 OPC RW 应用组的 EH 有所减少。相反，OPC 100 mg/kg 全身应用组的 EH 增加。在第二个系列中，非 OPC、OPC 10 mg/kg 全身给药组和 OPC RW 应用组之间，p-VP 水平和 p-OSM 均无显着差异。然而，在OPC 100 mg/kg全身应用组中，p-VP水平显着高于其他组，并且p-OSM高于非OPC组。低剂量 OPC 的全身应用和 OPC 的局部应用导致 EH 降低，但全身效应最小（p-VP 和 p-OSM）。这些发现表明 OPC-41061 可能是 EH 的一种有用的治疗选择。 (C) 2015 Elsevier B.V. 保留所有权利。
We investigated the influence of vasopressin type 2 receptor antagonist (OPC-41061; Tolvaptan) on experimentally induced endolymphatic hydrops (EH) in guinea pigs. In the first series, the endolymphatic sac (ES) of the left ear of all animals was electrocauterized. Four weeks after surgery, the animals were allocated to four groups: three systemic applications groups (saline, OPC 10 and 100 mg/kg) and a local round window (RW) OPC 1 mg/body application group. We examined the histopathology of the temporal bones and assessed volumetric changes of the endolymphatic space in the cochlea and saccule. In the second series, we investigated the effects of systemic and topical applications of OPC on plasma vasopressin (p-VP) concentrations and plasma osmolality (p-OSM). In the first series, we found that EH was reduced in the OPC 10 mg/kg systemic and OPC RW application groups. In contrast, EH increased in the OPC 100 mg/kg systemic application group. In the second series, neither p-VP levels nor p-OSM were significantly different among the non-OPC, OPC 10 mg/kg systemic, and OPC RW application groups. However, in the OPC 100 mg/kg systemic application group, the p-VP level was significantly higher than that in other groups, and p-OSM was higher than that in the non-OPC group. The systemic application of a low dose of OPC and topical application of OPC resulted in reduced EH in the face of minimal systemic effects (p-VP and p-OSM). These findings suggest that OPC-41061 may be one useful treatment option for EH. (C) 2015 Elsevier B.V. All rights reserved.