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Tolvaptan induces body fluid loss and subsequent water conservation in normal rats
- Source :
- Journal of Pharmacological Sciences, Vol 149, Iss 3, Pp 115-123 (2022)
- Publication Year :
- 2022
- Publisher :
- Elsevier, 2022.
-
Abstract
- 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.
Details
- Language :
- English
- ISSN :
- 13478613
- Volume :
- 149
- Issue :
- 3
- Database :
- Directory of Open Access Journals
- Journal :
- Journal of Pharmacological Sciences
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.90507d2958e94da8acdfb4d5f3871b25
- Document Type :
- article
- Full Text :
- https://doi.org/10.1016/j.jphs.2022.04.008