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 Blood samples (0.35 ml) were withdrawn at baseline and 10 min after each infusion.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.
Zaretsky
Dmitry V
DV
Department of Emergency Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, USA. dzaretsk@iupui.edu
Molosh
Andrei I
AI
Zaretskaia
Maria V
MV
Rusyniak
Daniel E
DE
DiMicco
Joseph A
JA
D000324:Adrenocorticotropic Hormone / Q000097:blood*; D000704:Analysis of Variance; D018686:Anesthetics, Intravenous / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001769:Blood / Q000187:drug effects* / Q000378:metabolism; D004234:Diuretics, Osmotic / Q000008:administration & dosage / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects; D008297:Male; D008353:Mannitol / Q000008:administration & dosage / Q000494:pharmacology; D009994:Osmolar Concentration; D010913:Pituitary-Adrenal System / Q000187:drug effects; D011863:Radioimmunoassay; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D014520:Urethane / Q000008:administration & dosage / Q000494:pharmacology*
D018686:Anesthetics, Intravenous; D004234:Diuretics, Osmotic; D014520:Urethane; D008353:Mannitol; D000324:Adrenocorticotropic Hormone
J Pharmacol Toxicol Methods. 2009 Jan-Feb;59(1):13-20
18973819
Anesth Analg. 2002 Feb;94(2):313-8, table of contents
11812690
Eur J Pharmacol. 1999 Aug 13;378(3):311-6
10493107
Brain Res. 1993 Dec 10;630(1-2):262-70
8118692
Brain Res Bull. 1993;32(6):567-72
8221154
Experientia. 1986 Feb 15;42(2):109-14
2868911
Neuroscience. 2010 Feb 3;165(3):976-83
19896521
Biochem Pharmacol. 1966 Jun;15(6):729-34
5963904
Neuroendocrinology. 1974;14(3):151-64
4853652
Neurosci Lett. 2006 Apr 24;397(3):291-6
16406311
Lab Anim. 2002 Apr;36(2):105-14
11943074
J Neuroendocrinol. 2001 Jul;13(7):596-607
11442774
Anesth Analg. 2002 Feb;94(2):241-2
11812676
Masui. 1993 Apr;42(4):552-6
8391089
Endocrinology. 1991 Jan;128(1):331-40
1846102
Neuroendocrinology. 1999 May;69(5):352-9
10343176
Stress. 2004 Jun;7(2):75-83
15512850
Regul Pept. 1986 Apr;14(2):125-32
3012659
Br J Pharmacol. 1988 Jul;94(3):647-52
2846107
Endocrinology. 1989 Jun;124(6):3102-8
2542009
Toxicol Appl Pharmacol. 1983 May;68(3):354-8
6857669
Arch Int Pharmacodyn Ther. 1975 Oct;217(2):257-75
1190921
Pharmacology. 1981;22(4):209-26
7022489
Experientia. 1986 Mar 15;42(3):292-7
3007197
Am J Physiol Heart Circ Physiol. 2009 Nov;297(5):H1661-72
19749166
Acta Endocrinol (Copenh). 1984 Jul;106(3):362-7
6331038
Jpn J Pharmacol. 1989 Apr;49(4):523-7
2498560
Am J Physiol Regul Integr Comp Physiol. 2009 Mar;296(3):R831-43
19129373
J Pharm Pharmacol. 1964 Sep;16:603-10
14234871
Experientia. 1986 May 15;42(5):531-7
3519271
Aust J Biol Sci. 1987;40(1):91-6
3274655
J Pharmacol Exp Ther. 1982 Nov;223(2):524-35
6127404
J Clin Endocrinol Metab. 1997 Apr;82(4):1243-7
9100602
Br J Pharmacol Chemother. 1965 Jun;24:752-8
14340929