Increase in plasma ACTH induced by urethane is not a consequence of hyperosmolality

Although anesthetic doses of urethane increase plasma levels of ACTH, the exact mechanism through which this occurs is unclear. We theorized that these increases might be a consequence of an increased systemic osmolality owing to the large doses of urethane usually employed. To evaluate this possibility, we measured plasma osmolality and ACTH in a total of six rats after graded infusions of urethane (N=3 rats) or equimolar amounts of mannitol (N=3 rats). Rats received infusions at 15 min intervals up to a cumulative dose equivalent to an anesthetic dose for urethane (1.4 g/kg). Blood samples (0.35 ml) were withdrawn at baseline and 10 min after each infusion. Urethane and mannitol produced significant and equivalent increases in plasma osmolality. However, only urethane evoked increases in plasma ACTH which were maximal (252+/-55 pg/ml from a baseline of 27+/-7 pg/ml) after a cumulative dose of 1 g/kg. Thus, increases in plasma ACTH seen after anesthetic doses of urethane are unlikely to be a consequence of its effect on plasma osmolality.