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Tolvaptan induces body fluid loss and subsequent water conservation in normal rats 木戸口, 慧 キドグチ, サトシ Kidoguchi, Satoshi Kitada, Kento 北田, 研人 キタダ, ケント 藤澤, 良秀 フジサワ, ヨシヒデ Fujisawa, Yoshihide 中野, 大介 ナカノ, ダイスケ Nakano, Daisuke Nishiyama, Akira 西山, 成 ニシヤマ, アキラ Tolvaptan Body fluid Urea Cardiovascular energy expenditure Blood pressure 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 V2 receptor 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. journal article 日本薬理学会 Japanese Pharmacological Society 2022-07 VoR text/html Journal of pharmacological sciences 3 149 115 123 AA12022662 1347-8613 https://doi.org/10.1016/j.jphs.2022.04.008 https://kagawa-u.repo.nii.ac.jp/records/2000513 eng 35641024 https://doi.org/10.1016/j.jphs.2022.04.008 © 2022 The Authors. This is an open access article under the CC BY-NC-ND license. open access