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Prolonged exercise alters beta-adrenergic responsiveness in healthy sedentary humans
Abstract
To examine whether beta-adrenergic desensitization occurs after prolonged exercise, echocardiograms, heart rate responses to isoproterenol, plasma catecholamines, and circulating lymphocyte beta-adrenergic receptors were examined in 10 sedentary normal subjects at rest and after brief (10 min) and exhaustive (mean duration 95 min) cycle exercise. Resting end-diastolic volume and ejection fraction were significantly reduced after exercise (from 120 +/- 34 to 100 +/- 26 ml and from 60 +/- 0.4 to 54 +/- 0.6%, respectively; both P < 0.05). The amount of isoproterenol needed to increase heart rate 15 and 25 beats/min increased in a dose- (exercise duration) related fashion, and the increase in amount of isoproterenol needed after prolonged exercise was closely related to the decrease in ejection fraction (r2 = 0.67, P = 0.004). Circulating lymphocyte beta-receptor density and affinity, agonist binding, and adenylylcyclase levels were unchanged with prolonged exercise. In conclusion, prolonged exercise in sedentary normal subjects resulted in reduced cardiac chronotropic responsiveness to isoproterenol that was not reflected in peripheral lymphocyte beta-adrenergic-receptor downregulation.
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Exposure to beta-adrenergic agonists in humans may lead to attenuation of beta-adrenergic receptor responses.
“previous reports showing that exposure to betaadrenergic agonists in humans may lead to attenuation of beta-adrenergic receptor responses (35, 36)”
From Plasma Epinephrine Contributes to the Development of Experimental Hypoglycemia-Associated Autonomic Failure (2020) · cites this paper as [36]
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Goldspink, D. F. (2005) · Ergonomics · doi:10.1080/00140130500101247 · Cited by 177
“This could conceivably be because exercise increases the circulating levels of catecholamines and these are known to desensitize and/or downregulate b-adrenergic receptors (Eysmann et al. 1996).”
BackgroundLeft Ventricular Function Immediately following Prolonged Exercise
Middleton, N., Shave, R., George, K., Whyte, G. P., Hart, E. C., & Atkinson, G. (2006) · Medicine & Science in Sports & Exercise · doi:10.1249/01.mss.0000210203.10200.12 · Cited by 148
“Exercise‐Induced Cardiac Fatigue”—A Review of the Echocardiographic Literature
Oxborough, D., Birch, K. M., Shave, R., & George, K. (2010) · Echocardiography · doi:10.1111/j.1540-8175.2010.01251.x · Cited by 115
Cardiomyocyte Death and the Ageing and Failing Heart
Goldspink, D. F., Burniston, J. G., & Tan, L. (2003) · Experimental Physiology · doi:10.1113/eph8802549 · Cited by 109
Does the Human Heart Fatigue Subsequent to Prolonged Exercise?
Dawson, E. A., George, K., Shave, R., Whyte, G. P., & Ball, D. R. (2003) · Sports Medicine · doi:10.2165/00007256-200333050-00003 · Cited by 108
Hypoxia and the cardiovascular response to dynamic knee-extensor exercise
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“Other factors that might impair active relaxation include an alteration of β-adrenergic responsiveness with prolonged exercise (Eysmann et al. 1996).”
BackgroundResultLeft ventricular adaptations following short-term endurance training
Goodman, J. M., Liu, P. P., & Green, H. J. (2004) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00258.2004 · Cited by 99
“(18) recently failed to detect systolic impairment during 150 min of steady-state exercise, earlier and recent studies by others conducted in field conditions have reported declines in filling and contractile performance (12, 27, 45, 47).”
ResultImpact of marathon running on cardiac structure and function in recreational runners
Whyte, G. P., George, K., Shave, R., Dawson, E. A., Stephenson, C. E., Edwards, B., Gaze, D. C., Oxborough, D., Forster, J., & SIMSPON, R. (2004) · Clinical Science · doi:10.1042/cs20040186 · Cited by 96
Earnest, C. P., Jurča, R., Church, T. S., Chicharro, J. L., Hoyos, J., & Lucía, A. (2004) · British Journal of Sports Medicine · doi:10.1136/bjsm.2003.005140 · Cited by 91
Hart, E. C., Dawson, E. A., Rasmussen, P. V., George, K., Secher, N. H., Whyte, G. P., & Shave, R. (2006) · The Journal of Physiology · doi:10.1113/jphysiol.2006.116426 · Cited by 91
“A reduced chronotropic response to the β-AR agonist isoproterenol has been demonstrated following prolonged exercise in both untrained (Eysmann et al. 1996) and trained subjects (Douglas et al. 1998).”
BackgroundInfluentialShave, R., & Oxborough, D. (2012) · Progress in Cardiovascular Diseases · doi:10.1016/j.pcad.2012.01.007 · Cited by 68
Welsh, R. C., Warburton, D. E. R., Humen, D. P., et al. (2005) · The Journal of Physiology · doi:10.1113/jphysiol.2005.096412 · Cited by 60
“…with prolonged strenuous exercise may lead to decreased cardiac β-receptor function or desensitization through downregulation or uncoupling, with subsequent diminished chronotropic response and inferentially LV contractility (Friedman et al. 1987; Hammond et al. 1987; Eysmann et al. 1996).”
BackgroundResultInfluentialBanks, L., Sasson, Z., Busato, M., & Goodman, J. M. (2009) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00898.2009 · Cited by 58
“A reduction in -adrenergic sensitivity following PE has been reported by others (12, 19, 36, 37, 42); however, this is the first study to examine the contribution of exercise intensity and NA to this phenomenon.”
BackgroundMechanisms Underpinning Exercise-Induced Changes in Left Ventricular Function
Scott, J. M., & Warburton, D. E. R. (2008) · Medicine & Science in Sports & Exercise · doi:10.1249/mss.0b013e318172cf10 · Cited by 54
Scott, J. M., Esch, B. T. A., Haykowsky, M. J., Isserow, S., Koehle, M. S., Hughes, B., Zbogar, D., Bredin, S. S. D., McKenzie, D. C., & Warburton, D. E. R. (2006) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00641.2006 · Cited by 50
“As previously described (10, 11, 18, 25, 45), the slopes describing the linear stimulus-response relationship between the dose of dobutamine vs.”
BackgroundInfluentialDonaldson, J. A., Wiles, J. D., Coleman, D. A., Papadakis, M., Sharma, R., & O’Driscoll, J. M. (2019) · Sports Medicine · doi:10.1007/s40279-019-01142-5 · Cited by 50
The effects of prolonged strenuous exercise on left ventricular function: A brief review
McGavock, J., Warburton, D. E. R., Taylor, D. A., Welsh, R. C., Quinney, H. A., & Haykowsky, M. J. (2002) · Heart & Lung · doi:10.1067/mhl.2002.126106 · Cited by 46
Genotype Related Differences in β2 Adrenergic Receptor Density and Cardiac Function
Snyder, E. M., Hulsebus, M. L., Turner, S. T., et al. (2006) · Medicine & Science in Sports & Exercise · doi:10.1249/01.mss.0000218144.02831.f6 · Cited by 46
Effect of heating on the hemodynamic responses to vasoactive agents
Massett, M. P., Lewis, S. J., & Kregel, K. C. (1998) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.1998.275.3.r844 · Cited by 46
“However, functional desensitization of b-adrenoceptors has been reported after a single bout of exercise in humans (5) and dogs (9).”
BackgroundCavalcante, P. A. M., Rica, R. L., Evangelista, A. L., Serra, A. J., Pontes, F. L., Kilgore, L., Baker, J. S., Bocalini, D. S., & Júnior, A. J. F. (2015) · Clinical Interventions in Aging · doi:10.2147/cia.s79625 · Cited by 45
A new perspective on cardiovascular drift during prolonged exercise
Souissi, A., Haddad, M., Dergaa, I., Saad, H. B., & Chamari, K. (2021) · Life Sciences · doi:10.1016/j.lfs.2021.120109 · Cited by 48
Benefit of physical fitness against inflammation in obesity: Role of beta adrenergic receptors
Hong, S., Dimitrov, S., Pruitt, C., Shaikh, F., & Beg, N. (2013) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2013.12.009 · Cited by 45
“, 1987), or not related to (Eysmann et al., 1996; Frey et al., 1989) the density of b-ARs on immune cells in both human and animal studies.”
InfluentialAshley, E. A., Kardos, A., Jack, E. S., Habenbacher, W., Wheeler, M. T., Kim, Y. M., Froning, J. N., MYERS, J. N., Whyte, G. P., Froelicher, V. F., et al. (2006) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2006.02.071 · Cited by 44
Self-citationAn Extreme Mountain Ultra-Marathon Decreases the Cost of Uphill Walking and Running
Vernillo, G., Savoldelli, A., Skafidas, S., Zignoli, A., Torre, A. L., Pellegrini, B., Giardini, G., Trabucchi, P., Millet, G. P., & Schena, F. F. (2016) · Frontiers in Physiology · doi:10.3389/fphys.2016.00530 · Cited by 50
“The vertical cost decreased by 10.4% (P 0.001, ES = −1.01 ± 0.31, moderate), 6.8% (P = 0.009, ES = −0.65 ± 0.32, moderate), and 6.7% (P = 0.01, ES = −0.62± 0.36,moderate) for the walking, grounded running, and running condition, respectively (Table 1).”
BackgroundInfluentialGenetics of β2-Adrenergic Receptors and the Cardiopulmonary Response to Exercise
Snyder, E. M., Johnson, B. D., & Joyner, M. J. (2008) · Exercise and Sport Sciences Reviews · doi:10.1097/jes.0b013e318168f276 · Cited by 36
“Another study found that lymphocyte ADRB2 density and affinity were unchanged in sedentary individuals after prolonged exercise; however, the amount of isoproterenol required to elevate heart rate after exercise increased relative to that required before exercise, suggesting receptor desensitization (9).”
BackgroundVitiello, D., Boissière, J., Doucende, G., Gayrard, S., Polge, A. S., Faure, P., Goux, A., Tanguy, S., Obert, P., Reboul, C., et al. (2011) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00449.2011 · Cited by 33
Lord, R. N., Utomi, V., Oxborough, D., Curry, B. A., Brown, M., & George, K. (2018) · European Journal of Applied Physiology · doi:10.1007/s00421-018-3906-z · Cited by 35
“A number of studies have suggested that the increased circulating catecholamines during prolonged exercise may result in decreased cardiac β-receptor function or desensitisation via downregulation and/or uncoupling with the subsequent reduction in LV inotropic and chronotropic response explaining LV dysfunction (Eysma…”
BackgroundGeorge, K., Dawson, E. A., Shave, R., et al. (2004) · British Journal of Sports Medicine · doi:10.1136/bjsm.2003.004788 · Cited by 27
Myocardial Dimensions and Hemodynamics during 24-h Ultraendurance Ergometry
Pokan, R., Ocenasek, H., Hochgatterer, R., Miehl, M., Vonbank, K., von DUVILLARD, S. P., Franklin, B. A., Würth, S., Volf, I., Wonisch, M., et al. (2013) · Medicine & Science in Sports & Exercise · doi:10.1249/mss.0b013e3182a64639 · Cited by 27
Mattsson, C. M., Enqvist, J. K., Brink-Elfegoun, T., Johansson, P. H., Bakkman, L., & Ekblom, B. T. (2009) · Scandinavian Journal of Medicine and Science in Sports · doi:10.1111/j.1600-0838.2009.00878.x · Cited by 27
“Instead, the results support the cardiac fatigue theory that the altered HR drift is due to desensitization of the heart’s adrenergic receptors caused by high concentrations of catecholamines (Friedman et al., 1987; Eysmann et al., 1996; Welsh et al., 2005; Hart et al., 2006).”
ResultHassan, M. Y., Noakes, T. D., Berlyn, P., et al. (2006) · British Journal of Sports Medicine · doi:10.1136/bjsm.2005.024745 · Cited by 27
Syncope is unrelated to supine and postural hypotension following prolonged exercise
Murrell, C., Cotter, J. D., George, K., Shave, R., Wilson, L. C., Thomas, K. N., Williams, M. J. A., & Ainslie, P. N. (2010) · European Journal of Applied Physiology · doi:10.1007/s00421-010-1671-8 · Cited by 20
“2007), and b-adrenergic receptors exhibit desensitisation to sympathetic activity (Eysmann et al. 1996; Hart et al. 2006); potentially evoking greater initial reductions in MAP upon postural change.”
BackgroundLate Cardiovascular Drift Observable during Ultraendurance Exercise
Mattsson, C. M., Ståhlberg, M., Larsen, F. J., et al. (2010) · Medicine & Science in Sports & Exercise · doi:10.1249/mss.0b013e318208f773 · Cited by 19
Lontchi-Yimagou, E., Aleksic, S., Hulkower, R., Gospin, R., Goyal, A., Kuo, B., Mitchell, W. G., You, J. Y., Upadhyay, L., Carey, M., et al. (2020) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgaa539 · Cited by 17
Modulation of adrenergic receptors and adrenergic functions in cold adapted humans
Janský, L., Vybíral, S., Trubačová, M., et al. (2007) · European Journal of Applied Physiology · doi:10.1007/s00421-007-0627-0 · Cited by 16
“Friedman et al. (1987) and Eysmann et al. (1996) suggested that prolonged exercise might be associated with functional desensitization of cardiac -receptors.”
BackgroundMenicucci, D., Piarulli, A., Mastorci, F., et al. (2013) · PubMed · doi:10.4449/aib.v151i3.1523 · Cited by 15
The effect of weightlifting upon left ventricular function and markers of cardiomyocyte damage
Stephenson, C. E., McCarthy, J., Vikelis, E., Shave, R., Whyte, G. P., Gaze, D. C., & George, K. (2005) · Ergonomics · doi:10.1080/00140130500101114 · Cited by 14
“It has also been reported that exercise down-regulates cardiac b-adrenergic receptors to below resting levels (Fraser et al. 1981) and that acute exercise can decrease cardiac chronotropic responsiveness to isoproterenol (Eysmann et al. 1996).”
BackgroundEffect of a 24-h continuous walking race on cardiac autonomic control
Cottin, F., SLAWINSKI, J. S., Lopes, P., et al. (2006) · European Journal of Applied Physiology · doi:10.1007/s00421-006-0341-3 · Cited by 14
“However, a plausible phenomenon which could contribute to the increase in LF/HF ratio is the concentration of the plasma catecholamines that increases during prolonged exercise (Eysmann et al. 1996).”
BackgroundMoving in extreme environments: extreme loading; carriage versus distance
Lucas, S. J. E., Helge, J. W., Schütz, U. H. W., Goldman, R. F., & Cotter, J. D. (2016) · Extreme Physiology & Medicine · doi:10.1186/s13728-016-0047-z · Cited by 13
“Research on prolonged, multiday military training indicates that chronic elevation of circulating noradrenaline may lead to a desensitisation to the sympathetic response [7, 8, 77, 122, 123], which has even been observed within one bout of exercise (36–135 min at 5–10 % below anaerobic threshold [124]).”
Backgroundde Galan, B. E., Rietjens, S. J., Tack, C. J., van der Werf, S. P., Sweep, C. G. J. (., W. M. Lenders, J., & Smits, P. (2003) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2003-030407 · Cited by 12
Effects of maturation and acute hypoxia on receptor-IP3coupling in ovine common carotid arteries
Angeles, D. M., Williams, J. M., Purdy, R. E., Zhang, L., & Pearce, W. J. (2001) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.2001.280.2.r410 · Cited by 12
POWERLIFTING SESSIONS PROMOTE SIGNIFICANT POST-EXERCISE HYPOTENSION
João, G. A., Bocalini, D. S., Rodríguez, D., Charro, M. A., Ceschini, F. L., Martins, A., & Júnior, A. J. F. (2017) · Revista Brasileira de Medicina do Esporte · doi:10.1590/1517-869220172302166667 · Cited by 11
The carotid baroreflex is reset following prolonged exercise in humans
Hart, E. C., Rasmussen, P., Secher, N. H., et al. (2010) · Acta Physiologica · doi:10.1111/j.1748-1716.2010.02160.x · Cited by 11
“Secondly, alterations in b-adrenergic receptor sensitivity have been demonstrated to explain part of the change in systolic function after prolonged exercise (Eysmann et al. 1996, Hart et al. 2006).”
BackgroundCardiac function following prolonged exercise: influence of age
Banks, L., Sasson, Z., Esfandiari, S., Busato, G., & Goodman, J. M. (2011) · Journal of Applied Physiology · doi:10.1152/japplphysiol.01242.2010 · Cited by 10
Menicucci, D., Piarulli, A., & MASTORCI, F. (2013) · ARCHIVES ITALIENNES DE BIOLOGIE · doi:10.12871/00039829201334 · Cited by 16
Left Ventricular Function Immediately following Prolonged Exercise: A Meta-Analysis
Shephard, R. J. (2007) · Yearbook of Sports Medicine · doi:10.1016/s0162-0908(08)70132-6 · Cited by 5
Sikri, G., Srinivasa, A., & Grewal, R. (2014) · PubMed · Cited by 2
PHYSIOLOGY OF ADVENTURE RACING - WITH EMPHASIS ON CIRCULATORY RESPONSE AND CARDIAC FATIGUE
Mattsson, C. M. (2011) · Diva portal (Dalarna University Library) · Cited by 2
Lord, R. N., Adams, Z. H., George, K., Somauroo, J. D., Jones, H., & Oxborough, D. (2023) · Echo Research and Practice · doi:10.1186/s44156-023-00035-8 · Cited by 2
“In support of this, human studies have consistently demonstrated that the cardiovascular response to a beta-adrenergic agonist (dobutamine) is reduced following a period of endurance exercise [2, 10, 12, 37], even under parasympathetic blockade [12].”
ResultRadić, P., Bulj, N., Car, S., Čančarević, M., Šikić, A., Delić-Brkljačić, D., Pavlov, M., & Babić, Z. (2025) · Journal of Clinical Medicine · doi:10.3390/jcm14072226 · Cited by 1
“The downregulation of beta-adrenergic receptors following prolonged exposure to increased levels of circulating catecholamines may be the culprit behind the reduction in LV contractility [15].”
Vigna, C. (2015) · UWSpace (University of Waterloo)
Scott, J. M. (2009) · cIRcle (University of British Columbia) · doi:10.14288/1.0077033
“(19) also examined lymphocyte preceptor density following prolonged exercise, but reported no differences between pre- and postexercising levels.”
BackgroundInfluential
Metadata
- Authors
- Eysmann, S. B., Gervino, E., Vatner, D. E., Katz, S. E., Decker, L., & Douglas, P. S.
- Affiliations
- Beth Israel Deaconess Medical Center (US)
- Venue
- Journal of Applied Physiology
- Publisher
- American Physiological Society
- Published
- 1996-02-01
- Volume
- 80
- Issue
- 2
- Pages
- 616-622
- ISSN
- 0161-7567 (ISSN-L)
- 8750-7587
- 1522-1601
- OpenAlex
- W2355952088
- Cited by
- 53
- References
- 0
- Citations by year
- 2025: 1 · 2023: 1 · 2021: 1 · 2020: 1 · 2019: 1 · 2018: 1 · 2017: 1 · 2016: 2 · 2015: 2 · 2014: 1 · 2013: 3 · 2012: 1
- FWCI
- 3.10
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Applied Physiology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (7r01hl037404-11, 5p01hl038070-07, 5r01hl045332-04)
- National Heart, Lung, and Blood Institute (HL38070, HL-45332, HL37404)
- Topics
- Health Sciences › Medicine › Physiology (medical) › Cardiovascular and exercise physiology
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Effects of Exercise
- Health Sciences › Medicine › Physiology (medical) › Exercise and Physiological Responses
- Keywords
- beta-adrenergic receptor desensitization, prolonged exercise, sedentary subjects, isoproterenol, heart rate response, ejection fraction, end-diastolic volume, catecholamines, exercise duration
- MeSH terms
- Adenylyl Cyclases, Adrenergic beta-Agonists, Adult, Catecholamines, Exercise Test, Female, Humans, Injections, Intravenous, Iodine Radioisotopes, Isoproterenol, Lymphocytes, Male, Middle Aged, Myocardium, Radioligand Assay, Receptors, Adrenergic, beta, Echocardiography, Doppler, Exercise, Down-Regulation, Ventricular Function, Left
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