title: Dissociation between changes in plasma bioactive and immunoreactive adrenocorticotropin after hemorrhage in awake dogs.
abstract: 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.
authors.affiliation: Department of Surgery, Brown University/Rhode Island Hospital, Providence 02903.
authors.forename: W C
authors.initials: WC
authors.lastname: Engeland
authors.forename: P
authors.initials: P
authors.lastname: Miller
authors.forename: D S
authors.initials: DS
authors.lastname: Gann
mesh_terms: D000302:Adrenal Cortex / Q000187:drug effects / Q000378:metabolism; D000311:Adrenal Glands / Q000098:blood supply; D000324:Adrenocorticotropic Hormone / Q000097:blood* / Q000276:immunology / Q000494:pharmacology; D000818:Animals; D001681:Biological Assay / Q000379:methods; D001794:Blood Pressure; D003345:Corticosterone / Q000378:metabolism; D004285:Dogs; D006339:Heart Rate; D006470:Hemorrhage / Q000097:blood* / Q000503:physiopathology; D006854:Hydrocortisone / Q000097:blood; D008297:Male; D011863:Radioimmunoassay / Q000379:methods; D051381:Rats; D012016:Reference Values; D012039:Regional Blood Flow
chemical_list: D000324:Adrenocorticotropic Hormone; D003345:Corticosterone; D006854:Hydrocortisone