Advisor(s)
Kelly Hyndman
Committee Member(s)
David Pollock
Malgorzata Kasztan
School
Joint Health Sciences (Interdisciplinary)
Document Type
Thesis
Department (new version)
Joint Health Sciences
Date of Award
1-6-2025
Abstract
Aquaporins (AQPs) are a family of proteins that play a major role in maintaining water homeostasis. Aquaporin 2 (AQP2) and aquaporin 3 (AQP3) are expressed in the collecting duct and regulated by the antidiuretic hormone arginine vasopressin (AVP) through the AVPR2 receptor. It is well known that biological circadian rhythms are critical for maintaining homeostasis. In both humans and rodents, the kidneys exhibit time-of-day-dependent changes in function. We hypothesized that there is a diurnal pattern in urine and/or plasma osmolality, and that this may reflect changes in kidney aquaporins in mice. Male and female C57BL/6J mice (10-11 weeks old) were euthanized in the middle of their active period (ZT18) or the middle of their inactive period (ZT6), and samples were collected. AVPR2 agonist (desmopressin, dDAVP) and antagonist (tolvaptan) were administered at ZT6 or ZT18 to determine if their potency on urine concentrating ability was dependent on the time of day. We found that in male and female mice there was significant diurnal variability in urine and plasma osmolality between ZT6 and ZT18, with higher urine and plasma osmolality occurring during the middle of the active period. However, the localization or abundance of aquaporins in the kidney at these time points did not show a diurnal pattern, except for AQP4 in female mice. The AVPR2 agonist dDAVP caused greater water reabsorption during the middle of the active period. However, the AVPR2 antagonist tolvaptan showed no diurnal potency on urine flow. Our data also support the existence of sex-specific effects on kidney AQPs and the potency of dDAVP and tolvaptan. This study identified the diurnal variability of urine concentrating ability and water homeostasis, which was not dependent on aquaporin abundance or localization. Moreover, the finding that the potency of dDAVP followed a diurnal rhythm provides important insights into the optimal timing for administering the medication to maximize efficacy and minimize complications. Additionally, our findings on sex differences in aquaporin abundance and the potency of dDAVP and tolvaptan in mice emphasize that there are sex-specific mechanisms that regulate fluid-electrolyte balance.
ProQuest ID
Recommended Citation
Nguyen, Phi Hung, "Diurnal Function And Expression Of Aquaporins In The Mouse Kidney" (2025). All ETDs from UAB. 7282.
https://digitalcommons.library.uab.edu/etd-collection/7282
