Abstract
To date no published data exist regarding the effects of chronic high-dose anabolic-androgenic steroid administration on tonic cardiac autonomic control. The aim of this study was to evaluate, by power spectral analysis of heart rate variability (HRV), the effects of chronic treatment with supraphysiological doses of nandrolone decanoate (DECA) on tonic cardiac autonomic regulation in sedentary rats. Male Wistar rats were treated weekly with 10 mg kg−1 of DECA (n=7) or vehicle (CONTROL, n=7) for 10 weeks. At the 8th week of treatment, electrocardiogram was recorded in the conscious state, for time- and frequency-domain HRV analysis. Parasympathetic indexes were reduced in DECA group: high-frequency power (CONTROL=11.1±3.0 ms² vs. DECA=3.8±0.6 ms², P<0.05), RMSSD (CONTROL=5.9±0.9 ms vs. DECA 3.5±0.3 ms; P<0.05) and pNN5 (CONTROL=31.5±7.5 ms vs. DECA=13.2±2.6 ms; P<0.05). The sympathetic index LF/HF tended to be higher in DECA group (CONTROL=0.65±0.15 vs. DECA=1.17±0.26, P=0.0546). In conclusion, chronic treatment with DECA, in rats, impairs tonic cardiac autonomic regulation, which may provide a key mechanism for anabolic steroid-induced arrhythmia and sudden cardiac death.
Similar content being viewed by others
References
Akselrod S, Gordon D, Ubel FA, Shannon DC, Berger AC, Cohen RJ (1981). Power spectrum analysis of heart rate fluctuation: a quantitative probe of beat-to-beat cardiovascular control. Science 213:220–222
Aubert AE, Ramaekers D, Beckers F, Breem R, Denef C, Van De Werf F, Ector H (1999) The analysis of heart rate variability in unrestrained rats. Validation of method and results. Comput Methods Programs Biomed 60:197–213
Bigger JT Jr, Fleiss JL, Steinman RC, Rolnitzky LM, Kleiger RE, Rottman JN (1992) Frequency-domain measures of heart period variability and mortality after myocardial infarction. Circulation 85:164–171
Bronson FH, Matherne CM (1997) Exposure to anabolic-androgenic steroids shortens life span of male mice. Med Sci Sports Exerc 29:615–619
Cohen MA, Taylor JA (2002) Short-term cardiovascular oscillations in man: measuring and modelling the physiologies. J Physiol 542:669–683
De Piccoli B, Giada F, Benettin A, Sartori F, Piccolo E (1991) Anabolic steroid use in body builders: an echocardiographic study of left ventricle morphology and function. Int J Sports Med 12:408–412
De Wardener HE (2001) The hypothalamus and hypertension. Physiol Rev 81:1599–1658
Dickerman RD, Schaller F, Prather I, McConathy WJ (1995) Sudden cardiac death in a 20-year-old bodybuilder using anabolic steroids. Cardiology 86:172–173
El-Mas MM, Abdel-Rahman AA (2004) Differential modulation by estrogen of alpha2-adrenergic and I1-imidazoline receptor-mediated hypotension in female rats. J Appl Physiol 97:1237–1244
Ferenchick GS, Adelman S (1992) Myocardial infarction associated with anabolic steroid use in a previously healthy 37-year-old weight lifter. Am Heart J 124:507–508
Fineschi V, Baroldi G, Monciotti F, Paglicci Reattelli L, Turillazzi E (2001) Anabolic steroid abuse and cardiac sudden death: a pathologic study. Arch Pathol Lab Med 125:253–255
Hamson DK, Jones BA, Watson NV (2004) Distribution of androgen receptor immunoreactivity in the brainstem of male rats. Neuroscience 127:797–803
Ishac EJ, Eskay R, Hirata F, Axelrod J, Kunos G (1987) Adrenergic regulation of beta-endorphin secretion from anterior pituitary in conscious rats: effects of thyroid state. Endocrinology 120:1073–1078
Joumaa WH, Léoty C (2001) Differential effects of nandrolone decanoate in fast and slow rat skeletal muscles. Med Sci Sports Exerc 33:397–403
Kennedy MC, Lawrence C (1993) Anabolic steroid abuse and cardiac death. Med J Aust 158:346–348
Kindlundh AMS, Lindblom J, Bergström L, Nyberg F (2003) The anabolic-andogenic steroid nandrolone induces alteration in the density of serotonergic 5HT1B and 5HT2 receptors in the male rat brain. Neuroscience 119:113–120
Kindlundh AMS, Rahman S, Lindblom J, Nyberg F (2004) Increased dopamine transporter density in the male rat brain following chronic nandrolone decanoate administration. Neurosci Lett 356:131–134
Kleiger RE, Miller JP, Bigger JT, Moss AJ, The Multicenter Post-Infarction Research Group (1987) Decreased heart rate variability and its association with increased mortality after acute myocardial infarction. Am J Cardiol 59:256–262
Krüger C, Landerer V, Zugck C, Ehmke H, Kubler W, Haass M (2000) The bradycardic agent zatebradine enhances baroreflex sensitivity and heart rate variability in rats early after myocardial infarction. Cardiovasc Res 45:900–912
LeGros T, McConnell D, Murry T, Edavettal M, Racey-Burns LA, Shepherd RE, Burns AH (2000) The effects of 17 alpha-methyltestosterone on myocardial function in vitro. Med Sci Sports Exerc 32:897–903
Levy MN (1971) Sympathetic-parasympathetic interactions in the heart. Circ Res 29:437–445
Liang MTC, Paulson DJ, Kopp SJ, Glonek T, Meneses P, Gierke LW, Schwartz FN (1993) Effects of anabolic steroids and endurance exercise performance. Int J Sports Med 14:324–329
Lindblom J, Kindlundh AMS, Nyberg F, Bergström L, Wikberg JES (2003) Anabolic androgenic steroid nandrolone decanoate reduces hypothalamic proopiomelanocortin mRNA levels. Brain Res 986:139–147
Maron BJ (1997) Hypertrophic cardiomyopathy. Lancet 350:127–133
McNutt RA, Ferenchick GS, Kirlin PC, Hamlin NJ (1988) Acute myocardial infarction in a 22-year-old world class weight lifter using anabolic steroids. Am J Cardiol 62:164
NIDA - National Institute on Drug Abuse. Research report series: Anabolic steroid abuse (2000) [Online]. U.S. Department of Health and Human Services, National Institutes of Health. http://www.nida.nih.gov/PDF/RRSteroi.pdf [14 Jul. 2004]
Norton GR, Trifunovic B, Woodiwiss AJ (2000) Attenuated beta-adrenoceptor-mediated cardiac contractile responses following androgenic steroid administration to sedentary rats. Eur J Appl Physiol 81:310–316
Parssinen M, Kujala U, Vartiainen E, Sarna S, Seppala T (2000) Increased premature mortality of competitive powerlifters suspected to have used anabolic agents. Int J Sports Med 21:225–227
Pavlatos AM, Fultz O, Monberg MJ, Vootkur A (2001) Review of oxymetholone: a 17α-alkylated anabolic-androgenic steroid. Clin Ther 23:789–801
Payne JR, Kotwinski PJ, Montgomery HE (2004) Cardiac effects of anabolic steroids. Heart 90:473–475
Pearson AC, Schiff M, Mrosek D, Labovitz AJ, Williams GA (1986) Left ventricular diastolic function in weight lifters. Am J Cardiol 58:1254–1259
Ramaekers D, Beckers F, Demeulemeester H, Aubert AE (2002a) Cardiovascular autonomic function in conscious rats: a novel approach to facilitate stationary conditions. Ann Noninvasive Electrocardiol 7:307–318
Ramaekers D, Beckers F, Demeulemeester H, Bert C, Denef C, Aubert AE (2002b) Effects of melanocortins on cardiovascular regulation in rats. Clin Exp Pharmacol Physiol 29:549–558
Routledge HC, Chowdhary S, Townend JN (2002) Heart rate variability–a therapeutic target? J Clin Pharm Ther 27:85–92
Sanyal SN, Ono K (2002) Derangement of autonomic nerve control in rat with right ventricular failure. Pathophysiology 8:197–203
Sanyal SN, Arita M, Ono K (2002) Inhomogeneous derangement of cardiac autonomic nerve control in diabetic rats. Circ J 66:283–288
Schänzer W (1996) Metabolism of anabolic androgenic steroids. Clin Chem 42:1001–1020
Schlussman SD, Zhou Y, Johansson P, Kiuru A, Ho A, Nyberg F, Kreek MJ (2000) Effects of the androgenic anabolic steroid, nandrolone decanoate, on adrenocorticotropin hormone, corticosterone and proopiomelanocortin, corticotrophin releasing factos (CRF) and CRF receptor1 mRNA levels in the hypothalamus, pituitary and amygdala of the rat. Neurosci Lett 284:190–194
Strauss RH, Yesalis CE (1991) Anabolic steroids in the athlete. Annu Rev Med 42:449–457
Sullivan ML, Martinez CM, Gennis P, Gallagher EJ (1998) The cardiac toxicity of anabolic steroids. Prog Cardiovasc Dis 41:1–15
Takahashi M, Tatsugi Y, Kohno T (2004) Endocrinological and pathological effects of anabolic-androgenic steroid in male rats. Endocr J 51:425–434
Tamaki T, Shiraishi T, Takeda H, Matsumiya T, Roy RR, Edgerton VR (2003) Nandrolone decanoate enhances hypothalamic biogenic amines in rats. Med Sci Sports Exerc 35:32–38
Task Force of the European Society of Cardiology, the North American Society of Pacing and Electrophysiology (1996) Heart rate variability: standards of measurement, physiological interpretantion and clinical use. Circulation 93:1043–1065
Thiblin I, Finn A, Ross SB, Stenfors C (1999) Increased dopaminergic and 5-hydroxytryptaminergic activities in male rat brain following long-term treatment with anabolic androgenic steroids. Br J Pharmacol 126:1301–1306
Thompson PD, Sadaniantz A, Cullinane EM, Bodziony KS, Catlin DH, Torek-Both G, Douglas PS (1992) Left ventricular function is not impaired in weight-lifters who use anabolic steroids. J Am Coll Cardiol 19:278–282
Trifunovic B, Norton GR, Duffield MJ, Avraam P, Woodiwiss AJ (1995) An androgenic steroid decreases left ventricular compliance in rats. Am J Physiol 268:H1096–1105
Tsuji H, Larson MG, Venditti FJ Jr, Manders ES, Evans JC, Feldman CL, Levy D (1996) Impact of reduced heart rate variability on risk for cardiac events—the Framingham heart study. Circulation 94:2850–2855
Urhausen A, Albers T, Kinderman W (2004) Are the cardiac effects of anabolic steroid abuse in strength athletes reversible? Heart 90:496–501
Woodiwiss AJ, Trifunovic B, Philippides M, Norton GR (2000) Effects of an androgenic steroid on exercise-induced cardiac remodeling in rats. J Appl Physiol 88:409–415
Acknowledgements
PPPJ was recipient of a CNPq scholarship, and this work is part of his MSc manuscript.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Pereira-Junior, P.P., Chaves, E.A., Costa-e-Sousa, R.H. et al. Cardiac autonomic dysfunction in rats chronically treated with anabolic steroid. Eur J Appl Physiol 96, 487–494 (2006). https://doi.org/10.1007/s00421-005-0111-7
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00421-005-0111-7