The ethanol metabolite acetaldehyde induces water and salt intake via two distinct pathways in the central nervous system of rats
The ethanol metabolite acetaldehyde induces water and salt intake via two distinct pathways in the central nervous system of rats
复制标题
乙醇代谢物乙醛通过大鼠中枢神经系统中的两种不同途径诱导水和盐的摄入
DOI：
10.1016/j.neuropharm.2015.08.023
复制
发表时间：
2015
影响因子：
4.7
通讯作者：
Inenaga K
中科院分区：
文献类型：
--
作者：
Ujihara I;Hitomi S;Ono K;Kakinoki Y;Hashimoto H;Ueta Y;Inenaga K
大量饮酒后的口渴感被广泛认为是乙醇（EtOH）诱导的利尿的结果，但高剂量的EtOH实际上会诱导抗利尿。本研究以大鼠为研究对象，以乙醇的代谢产物、毒性物质乙醛为研究对象，探讨了大量饮酒后水盐摄入的导入机制。醛脱氢酶（ALDH）抑制剂氰胺用于模拟乙醛长期暴露的效果，因为乙醛被ALDH快速降解。全身给予2.5 g/kg高剂量EtOH诱导水和盐摄入，并具有抗利尿作用。氰胺增强了乙醇和乙醛给药后的液体摄入量。乙醛和氰胺的全身给药抑制血压和增加血浆肾素活性。阻断中枢血管紧张素受体AT 1 R可抑制乙酰丙酮化物诱导的液体摄入和脑室周围器官（CVOs）中c-Fos的表达，这是脑中致渴机制的一部分。此外，中央管理的乙醛与氨腈一起选择性地诱导水，而不是盐的摄入量没有变化的血压。在从切片制备的电生理记录中，乙醛特异性地激发CVO中的血管紧张素敏感神经元。这些结果表明，乙醛引起口渴的感觉后，大量饮酒，由两个不同的和以前未知的机制，独立的利尿。首先，乙醛通过降压反应后的外周肾素-血管紧张素系统间接激活致渴中枢的AT 1 R，并诱导水和盐的摄入。其次，乙醛直接激活致渴中枢的神经元，只引起水的摄入。
The sensation of thirst experienced after heavy alcohol drinking is widely regarded as a consequence of ethanol (EtOH)-induced diuresis, but EtOH in high doses actually induces anti-diuresis. The present study was designed to investigate the introduction mechanism of water and salt intake after heavy alcohol drinking, focusing on action of acetaldehyde, a metabolite of EtOH and a toxic substance, using rats. The aldehyde dehydrogenase (ALDH) inhibitor cyanamide was used to mimic the effect of prolonged acetaldehyde exposure because acetaldehyde is quickly degraded by ALDH. Systemic administration of a high-dose of EtOH at 2.5 g/kg induced water and salt intake with anti-diuresis. Cyanamide enhanced the fluid intake following EtOH and acetaldehyde administration. Systemic administration of acetaldehyde with cyanamide suppressed blood pressure and increased plasma renin activity. Blockade of central angiotensin receptor AT1R suppressed the acetaldehyde-induced fluid intake and c-Fos expression in the circumventricular organs (CVOs), which form part of dipsogenic mechanism in the brain. In addition, central administration of acetaldehyde together with cyanamide selectively induced water but not salt intake without changes in blood pressure. In electrophysiological recordings from slice preparations, acetaldehyde specifically excited angiotensin-sensitive neurons in the CVO. These results suggest that acetaldehyde evokes the thirst sensation following heavy alcohol drinking, by two distinct and previously unsuspected mechanisms, independent of diuresis. First acetaldehyde indirectly activates AT1R in the dipsogenic centers via the peripheral renin-angiotensin system following the depressor response and induces both water and salt intake. Secondly acetaldehyde directly activates neurons in the dipsogenic centers and induces only water intake.