Stress triggers crucial responses, including elevated blood pressure and heart rate (HR), to handle the emergency and restore homeostasis. However, continuation of these effects following cessation of the stress is implicated with many stress-related disorders. Here, we examine the kinetics and persistence of cardiovascular and locomotor responses to single and repeated immobilization stress (IMO), with and without prior treatment with adrenocorticotropic hormone (ACTH). Radiotelemetry probes were implanted into male Sprague-Dawley rats to continually monitor mean arterial pressure (MAP), HR and locomotor activity. Rats were subjected to IMO for 2 h daily (10 a.m. to noon, 6 consecutive days). The first IMO induced the greatest change in MAP (about 30 mm Hg) and HR (about 200 bpm). Following each IMO, MAP and HR were elevated during the remaining light phase and in the subsequent dark phase, HR was lower than prior to IMO. We further examined whether elevation of ACTH to a level similar to IMO will elicit similar effects, and if it will alter subsequent responses to IMO. Injection of ACTH (13 IU/kg, s.c.) triggered a short-lived rise in MAP, and decreased HR. After six daily injections of ACTH and recovery time (8 days), rats were immobilized as above. The cardiovascular responses were similar during the IMO, but the ACTH-pretreated group displayed differences following cessation of the IMO. In addition, IMO led to a large reduction of locomotor activity during the dark (normally active) phase to levels similar to the light phase. Following the IMOs, locomotor activity recovered more slowly in the ACTH-pretreated group. The study revealed that IMO-triggered cardiovascular and locomotor responses are evident after termination of the stress. In addition, prior exposure to ACTH delayed recovery in cardiovascular and locomotor functions following cessation of stress.

Keywords:
Adrenocorticotropic hormone, Blood pressure, Heart rate, Locomotion, Radiotelemetry, Stress
1.
Selye H: The Stress of Life. New York, McGraw Hill, 1975.
2.
Chrousos GP, Gold PW: The concepts of stress and stress system disorders. Overview of physical and behavioral homeostasis. JAMA 1992;267:1244–1252.
3.
McEwen BS: Protective and damaging effects of stress mediators. N Engl J Med 1998;338:171–179.
4.
Goldstein DS: Stress, Catecholamines and Cardiovascular Disease. Oxford, Oxford University Press, 1995.
5.
Axelrod J, Reisine TD: Stress hormones: their interaction and regulation. Science 1984;224:452–459.
6.
Kvetnansky R, Mikulaj L: Adrenal and urinary catecholamines in rats during adaptation to repeated immobilization stress. Endocrinology 1970;87:738–743.
7.
Kvetnansky R, Pacak K, Fukuhara K, et al: Sympathoadrenal system in stress. Interaction with the hypothalamic-pituitary-adrenocortical system. Ann NY Acad Sci 1995;771:131–158.
8.
Goldstein DS: Catecholamines and stress. Endocr Regul 2003;37:69–80.
9.
Aguilera G: Regulation of pituitary ACTH secretion during chronic stress. Front Neuroendocrinol 1994;15:321–350.
10.
Nankova B, Kvetnansky R, Hiremagalur B, Sabban B, Rusnak M, Sabban EL: Immobilization stress elevates gene expression for catecholamine biosynthetic enzymes and some neuropeptides in rat sympathetic ganglia: effects of adrenocorticotropin and glucocorticoids. Endocrinology 1996;137:5597–5604.
11.
Nankova BB, Kvetnansky R, Sabban EL: Adrenocorticotropic hormone (MC-2) receptor mRNA is expressed in rat sympathetic ganglia and up-regulated by stress. Neurosci Lett 2003;344:149–152.
12.
Versteeg DH, Van Bergen P, Adan RA, De Wildt DJ: Melanocortins and cardiovascular regulation. Eur J Pharmacol 1998;360:1–14.
13.
Whitworth JA, Hewitson TD, Ming L, et al: Adrenocorticotrophin-induced hypertension in the rat: haemodynamic, metabolic and morphological characteristics. J Hypertens 1990;8:27–36.
14.
Kawabe T, Chitravanshi VC, Kawabe K, Sapru HN: Cardiovascular effects of adrenocorticotropin microinjections into the rostral ventrolateral medullary pressor area of the rat. Brain Res 2006;1102:117–126.
15.
Brown S, Chitravanshi VC, Sapru HN: Cardiovascular actions of adrenocorticotropin microinjections into the nucleus tractus solitarius of the rat. Neuroscience 2006;143:863–874.
16.
Torpy DJ, Mullen N, Ilias I, Nieman LK: Association of hypertension and hypokalemia with Cushing’s syndrome caused by ectopic ACTH secretion: a series of 58 cases. Ann NY Acad Sci 2002;970:134–144.
17.
Kvetnansky R, Fukuhara K, Pacak K, Cizza G, Goldstein DS, Kopin IJ: Endogenous glucocorticoids restrain catecholamine synthesis and release at rest and during immobilization stress in rats. Endocrinology 1993;133:1411–1419.
18.
McDougall SJ, Lawrence AJ, Widdop RE: Differential cardiovascular responses to stressors in hypertensive and normotensive rats. Exp Physiol 2005;90:141–150.
19.
Chen X, Herbert J: Regional changes in c-fos expression in the basal forebrain and brainstem during adaptation to repeated stress: correlations with cardiovascular, hypothermic and endocrine responses. Neuroscience 1995;64:675–685.
20.
Ely DL: Organization of cardiovascular and neurohumoral responses to stress. Implications for health and disease. Ann NY Acad Sci 1995;771:594–608.
21.
Grippo AJ, Beltz TG, Johnson AK: Behavioral and cardiovascular changes in the chronic mild stress model of depression. Physiol Behav 2003;78:703–710.
22.
Valles A, Marti O, Armario A: Long-term effects of a single exposure to immobilization: A C-fos mRNA study of the response to the homotypic stressor in the rat brain. J Neurobiol 2006;66:591–602.
23.
Farah VM, Joaquim LF, Morris M: Stress cardiovascular/autonomic interactions in mice. Physiol Behav 2006;89:569–575.
24.
Lamprecht F, Williams RB, Kopin IJ: Serum dopamine-beta-hydroxylase during development of immobilization-induced hypertension. Endocrinology 1973;92:953–956.
25.
Holson RR, Scallet AC, Ali SF, Turner BB: ‘Isolation stress’ revisited: isolation-rearing effects depend on animal care methods. Physiol Behav 1991;49:1107–1118.
26.
Brockway BP, Mills PA, Azar SH: A new method for continuous chronic measurement and recording of blood pressure, heart rate and activity in the rat via radio-telemetry. Clin Exp Hypertens A 1991;13:885–895.
27.
Masineni SN, Chander PN, Singh GD, Powers CA, Stier CT Jr: Male gender and not the severity of hypertension is associated with end-organ damage in aged stroke-prone spontaneously hypertensive rats. Am J Hypertens 2005;18:878–884.
28.
Sepehrdad R, Chander PN, Oruene A, Rosenfeld L, Levine S, Stier CT Jr: Amiloride reduces stroke and renal injury in stroke-prone hypertensive rats. Am J Hypertens 2003;16:312–318.
29.
Sabban EL, Nankova BB, Serova LI, Kvetnansky R, Liu X: Molecular regulation of gene expression of catecholamine biosynthetic enzymes by stress: sympathetic ganglia versus adrenal medulla. Ann NY Acad Sci 2004;1018:370–377.
30.
Serova LI, Nankova BB, Feng Z, Hong JS, Hutt M, Sabban EL: Heightened transcription for enzymes involved in norepinephrine biosynthesis in the rat locus coeruleus by immobilization stress. Biol Psychiatry 1999;45:853–862.
31.
Stier CT Jr, Serova LI, Singh G, Sabban EL: Stress triggered rise in plasma aldosterone is lessened by chronic nicotine infusion. Eur J Pharmacol 2004;495:167–170.
32.
Sabban EL, Liu X, Serova L, Gueorguiev V, Kvetnansky R: Stress triggered changes in gene expression in adrenal medulla: transcriptional responses to acute and chronic stress. Cell Mol Neurobiol 2006;26:845–854.
33.
McMahon A, Kvetnansky R, Fukuhara K, Weise VK, Kopin IJ, Sabban EL: Regulation of tyrosine hydroxylase and dopamine beta-hydroxylase mRNA levels in rat adrenals by a single and repeated immobilization stress. J Neurochem 1992;58:2124–2130.
34.
Vahl TP, Ulrich-Lai YM, Ostrander MM, et al: Comparative analysis of ACTH and corticosterone sampling methods in rats. Am J Physiol Endocrinol Metab 2005;289:E823–E828.
35.
Hauger RL, Lorang M, Irwin M, Aguilera G: CRF receptor regulation and sensitization of ACTH responses to acute ether stress during chronic intermittent immobilization stress. Brain Res 1990;532:34–40.
36.
Bartolomucci A, Palanza P, Costoli T, et al: Chronic psychosocial stress persistently alters autonomic function and physical activity in mice. Physiol Behav 2003;80:57–67.
37.
Pardon MC, Gould GG, Garcia A, et al: Stress reactivity of the brain noradrenergic system in three rat strains differing in their neuroendocrine and behavioral responses to stress: implications for susceptibility to stress-related neuropsychiatric disorders. Neuroscience 2002;115:229–242.
38.
Mitra R, Jadhav S, McEwen BS, Vyas A, Chattarji S: Stress duration modulates the spatiotemporal patterns of spine formation in the basolateral amygdala. Proc Natl Acad Sci USA 2005;102:9371–9376.
39.
Kim KS, Han PL: Optimization of chronic stress paradigms using anxiety- and depression-like behavioral parameters. J Neurosci Res 2006;83:497–507.
40.
Van Bergen P, Kleijne JA, De Wildt DJ, Versteeg DH: Different cardiovascular profiles of three melanocortins in conscious rats; evidence for antagonism between gamma 2-MSH and ACTH-(1–24). Br J Pharmacol 1997;120:1561–1567.
41.
Fraser TB, Turner SW, Mangos GJ, Ludbrook J, Whitworth JA: Comparison of telemetric and tail-cuff blood pressure monitoring in adrenocorticotrophic hormone-treated rats. Clin Exp Pharmacol Physiol 2001;28:831–835.
42.
Cole CR, Foody JM, Blackstone EH, Lauer MS: Heart rate recovery after submaximal exercise testing as a predictor of mortality in a cardiovascularly healthy cohort. Ann Intern Med 2000;132:552–555.
43.
Morshedi-Meibodi A, Larson MG, Levy D, O’Donnell CJ, Vasan RS: Heart rate recovery after treadmill exercise testing and risk of cardiovascular disease events (The Framingham Heart Study). Am J Cardiol 2002;90:848–852.
44.
Schneider GM, Jacobs DW, Gevirtz RN, O’Connor DT: Cardiovascular haemodynamic response to repeated mental stress in normotensive subjects at genetic risk of hypertension: evidence of enhanced reactivity, blunted adaptation, and delayed recovery. J Hum Hypertens 2003;17:829–840.
45.
Dallman MF, Strack AM, Akana SF, et al: Feast and famine: critical role of glucocorticoids with insulin in daily energy flow. Front Neuroendocrinol 1993;14:303–347.
46.
Grünfeld J: Glucocorticoids in blood pressure regulation. Horm Res 1990;34:111–113.
47.
Whitworth JA, Brown MA, Kelly JJ, Williamson PM: Mechanisms of cortisol-induced hypertension in humans. Steroids 1995;60:76–80.
48.
Darlington DN, Kaship K, Keil LC, Dallman MF: Vascular responsiveness in adrenalectomized rats with corticosterone replacement. Am J Physiol 1989;256:H1274–H1281.
49.
van den Buuse M, van Acker SA, Fluttert MF, de Kloet ER: Involvement of corticosterone in cardiovascular responses to an open-field novelty stressor in freely moving rats. Physiol Behav 2002;75:207–215.
50.
Serova LI, Gueorguiev V, Cheng SY, Sabban EL: Adrenocorticotropic hormone elevates gene expression for catecholamine biosynthesis in rat superior cervical ganglia and locus coeruleus by an adrenal independent mechanism. Neuroscience 2008;153:1380–1389.
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