Tolvaptan induces body fluid loss and subsequent water conservation in normal rats
Tolvaptan induces body fluid loss and subsequent water conservation in normal rats
复制标题
托伐普坦诱导正常大鼠体液流失和随后的水分保存
DOI：
10.1016/j.jphs.2022.04.008
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发表时间：
2022
影响因子：
3.5
通讯作者：
Nishiyama Akira
中科院分区：
文献类型：
--
作者：
Kidoguchi Satoshi;Kitada Kento;Fujisawa Yoshihide;Nakano Daisuke;Yokoo Takashi;Titze Jens;Nishiyama Akira
我们最近报道，尿素渗透压相关的水保护系统在液体丢失模型中被激活，例如高盐诱导的尿钠排泄、肾损伤诱导的肾浓缩能力受损或皮肤屏障功能障碍诱导的经表皮水分丢失。该系统由多个器官的相互作用组成，包括肾尿素再循环、肝-肌肉尿素生成和心血管能量消耗的抑制。在这里，我们确定了托伐普坦（一种选择性血管加压素V2受体拮抗剂）诱导的药理学脱水对水资源保护的影响。我们评估了消耗对照饮食或含有0.1%托伐普坦的饮食的大鼠的水保护系统。托伐普坦在第1天增加尿量，但这种肾脏水分丢失随后逐渐减少。托伐普坦在第1天降低了体内水分和渗透压物质含量，但在第7天恢复正常。托伐普坦在第1天诱导体液丢失，第7天体液恢复与尿素转运蛋白A1相关的肾尿素再循环增加相关。托伐普坦不影响第1天和第7天的肝肌肉尿素生成，也不影响治疗期间的心血管能量消耗。因此，托伐普坦诱导的液体损失导致通过肾尿素再循环激活水保护系统。
We have recently reported that the urea osmolyte-associated water conservation system is activated in fluid loss models such as high salt-induced natriuresis, renal injury-induced impaired renal concentrating ability, or skin barrier dysfunction-induced transepidermal water loss. The system consists of the interaction of multiple organs including renal urea recycling, hepato-muscular ureagenesis, and suppression of cardiovascular energy expenditure. Here, we determined the effect of pharmacological fluid loss induced by tolvaptan, a selective vasopressin V2receptor antagonist, on water conservation. We evaluated the water conservation system in rats that consumed a control diet or a diet containing 0.1% tolvaptan. Tolvaptan increased urine volume on day 1, but this renal water loss then gradually decreased. Body water and osmolyte content were decreased by tolvaptan on day 1 but had normalized by day 7. Tolvaptan induced fluid loss on day 1, and the following restoration of body fluid on day 7 was associated with an increase in urea transporter A1-associated renal urea recycling. Tolvaptan did not affect hepato-muscular ureagenesis on day 1 and day 7, or cardiovascular energy expenditure during treatment. Thus, tolvaptan-induced fluid loss leads to activation of the water conservation system via renal urea recycling.