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Updated: Jun 13, 2026

In Vivo Luminal Measurement of Distension-Evoked Urothelial ATP Release in Rodents
Published on: September 7, 2022
Increase in plasma ACTH induced by urethane is not a consequence of hyperosmolality
Dmitry V Zaretsky1, Andrei I Molosh, Maria V Zaretskaia
1Department of Emergency Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, USA. dzaretsk@iupui.edu
Anesthetic doses of urethane increase adrenocorticotropic hormone (ACTH) but not due to increased plasma osmolality. Mannitol infusions increased osmolality similarly to urethane, yet did not elevate ACTH levels.
Area of Science:
- Anesthesiology
- Endocrinology
- Physiology
Background:
- Anesthetic doses of urethane are known to elevate plasma levels of adrenocorticotropic hormone (ACTH).
- The precise mechanism driving urethane-induced ACTH increases remains incompletely understood.
- A prevailing hypothesis suggests that increased systemic osmolality from urethane administration might be responsible.
Purpose of the Study:
- To investigate whether elevated plasma osmolality is the causative factor for urethane-induced ACTH release.
- To differentiate the effects of urethane on ACTH from the effects of osmolality changes alone.
Main Methods:
- Six rats were used, divided into two groups (N=3 per group).
- Graded infusions of urethane or equimolar mannitol were administered at 15-minute intervals.
- Plasma osmolality and ACTH levels were measured at baseline and after each infusion up to an anesthetic dose of urethane (1.4 g/kg).
Main Results:
- Both urethane and mannitol infusions caused significant and comparable increases in plasma osmolality.
- Only urethane administration led to substantial increases in plasma ACTH levels.
- Maximal ACTH elevations were observed after a cumulative urethane dose of 1 g/kg.
Conclusions:
- The observed increases in plasma ACTH following anesthetic urethane doses are unlikely to be a direct result of increased plasma osmolality.
- Urethane appears to stimulate ACTH release through a mechanism independent of systemic osmolality changes.
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