Endocrinology, Vol 124, 2978-2985, Copyright © 1989 by Endocrine Society

ARTICLES

Dissociation between changes in plasma bioactive and immunoreactive adrenocorticotropin after hemorrhage in awake dogs

WC Engeland, P Miller and DS Gann
Department of Surgery, Brown University/Rhode Island Hospital, Providence 02903.

The secretion of cortisol increases in awake dogs after small hemorrhage, with little or no change in plasma immunoreactive (IR) ACTH. To determined if IR-ACTH reflects bioactive (B) ACTH after hemorrhage, changes in B-ACTH and IR-ACTH were determined in awake dogs. Trained dogs were prepared with adrenal venous and femoral arterial and venous cannula. Experiments performed 48-96 h after surgery consisted of blood sampling from the adrenal vein and femoral artery before and after a 7.5-10 ml/kg hemorrhage done over 3 min. Cortisol was assayed by HPLC with UV detection, and adrenal secretory rates were calculated using adrenal blood flow. Arterial B-ACTH was assayed after extraction using rat adrenal cells dispersed with collagenase; corticosterone produced was assayed by HPLC-UV. Arterial IR-ACTH was assayed by RIA using antisera directed against ACTH-(1-24). Dogs in which hypotension occurred (change in mean arterial pressure, - 31 +/- 3; n = 6) were compared to dogs in which mean arterial pressure did not change (change in mean arterial pressure, -6 +/- 2; n = 5). In the absence of hypotension, B-ACTH increased by 10 min after the onset of hemorrhage coincident with increased cortisol secretion, whereas IR- ACTH did not increase until 20 min. Resting IR-ACTH was greater than B- ACTH (11 +/- 1 vs. 2 +/- 1 pg/ml), but the peak response of B-ACTH was greater than that of IR-ACTH (13 +/- 4 vs. 8 +/- 3 pg/ml). In the presence of hypotension, B-ACTH increased by 4 min, and IR-ACTH and cortisol secretion increased by 8 min after the onset of hemorrhage. Resting IR-ACTH was greater than B-ACTH (27 +/- 5 vs. 6 +/- 1 pg/ml), and the peak response of B-ACTH was less than that of IR-ACTH (64 +/- 26 vs. 112 +/- 33 pg/ml). In dogs subjected to blood sampling without hemorrhage (n = 4), resting IR-ACTH was greater than B-ACTH (34 +/- 5 vs. 5 +/- 1 pg/ml), but there was no change in B-ACTH, IR-ACTH, or cortisol secretion. The results show that small hemorrhage elicits changes in B-ACTH that are dissociated in time and magnitude from changes in IR-ACTH, are coincident with changes in cortisol secretion, and are greater in dogs that fail to maintain arterial pressure. These data indicate that B-ACTH predicts more accurately the change in cortisol secretion than does IR-ACTH after small hemorrhage.

This article has been cited by other articles:

				Y. M. Ulrich-Lai, M. M. Ostrander, I. M. Thomas, B. A. Packard, A. R. Furay, C. M. Dolgas, D. C. Van Hooren, H. F. Figueiredo, N. K. Mueller, D. C. Choi, et al. Daily Limited Access to Sweetened Drink Attenuates Hypothalamic-Pituitary-Adrenocortical Axis Stress Responses Endocrinology, April 1, 2007; 148(4): 1823 - 1834. [Abstract] [Full Text] [PDF]

				M. M. Ostrander, Y. M. Ulrich-Lai, D. C. Choi, N. M. Richtand, and J. P. Herman Hypoactivity of the Hypothalamo-Pituitary-Adrenocortical Axis during Recovery from Chronic Variable Stress Endocrinology, April 1, 2006; 147(4): 2008 - 2017. [Abstract] [Full Text] [PDF]

				D. A. Giussani, D. M. Farber, S. L. Jenkins, A. Yen, J. A. Winter, J. D. Tame, and P. W. Nathanielsz Opposing Effects of Androgen and Estrogen on Pituitary-Adrenal Function in Nonpregnant Primates Biol Reprod, May 1, 2000; 62(5): 1445 - 1451. [Abstract] [Full Text]

				R. A. Riquelme, J. A. Llanos, H. H. G. McGarrigle, E. M. Sanhueza, M. A. Hanson, and D. A. Giussani Chemoreflex Contribution to Adrenocortical Function during Acute Hypoxemia in the Llama Fetus at 0.6 to 0.7 of Gestation Endocrinology, May 1, 1998; 139(5): 2564 - 2570. [Abstract] [Full Text] [PDF]

				T. J. Zehnder, N. K. Valego, J. Schwartz, J. Green, and J. C. Rose Cortisol infusion depresses the ratio of bioactive to immunoreactive ACTH in adrenalectomized sheep fetuses Am J Physiol Endocrinol Metab, March 1, 1998; 274(3): E391 - E396. [Abstract] [Full Text] [PDF]

				H. C. Atkinson and B. J. Waddell Circadian Variation in Basal Plasma Corticosterone and Adrenocorticotropin in the Rat: Sexual Dimorphism and Changes across the Estrous Cycle Endocrinology, September 1, 1997; 138(9): 3842 - 3848. [Abstract] [Full Text] [PDF]

				R. F. McGivern, P. Rittenhouse, F. Aird, L. D. Van de Kar, and E. Redei Inhibition of Stress-Induced Neuroendocrine and Behavioral Responses in the Rat by Prepro-Thyrotropin-Releasing Hormone 178-199 J. Neurosci., June 15, 1997; 17(12): 4886 - 4894. [Abstract] [Full Text] [PDF]

				W. C. Engeland, B. K. Levay-Young, L. M. Rogers, and D. Fitzgerald Differential Gene Expression of Cytochrome P450 11{beta}-Hydroxylase in Rat Adrenal Cortex after in Vivo Activation Endocrinology, June 1, 1997; 138(6): 2338 - 2346. [Abstract] [Full Text] [PDF]

				J. R. Owiny, S. L. Jenkins, D. W. Sadowsky, and P. W. Nathanielsz Effect of Pulsatile Oxytocin Administration to the Pregnant Ewe in the Last Third of Gestation on Fetal ACTH and Cortisol Response to Acute Hypoxemia Reproductive Sciences, September 1, 1995; 2(5): 673 - 677. [Abstract] [PDF]

				J. R. Owiny, D. Sadowsky, S. Zarzeczny, and P. W. Nathanielsz Effect of Pulsatile Intravenous Oxytocin Administration to Pregnant Sheep Over the Last Third of Gestation on Fetal ACTH and Cortisol Responses to Hypotension Reproductive Sciences, January 1, 1995; 2(1): 13 - 18. [Abstract] [PDF]