© 2000 American Heart Association, Inc.
MiniReviews |
ß-Adrenergic Receptor Signaling: An Acute Compensatory Adjustment—Inappropriate for the Chronic Stress of Heart Failure?
Insights from Gs
Overexpression and Other Genetically Engineered Animal Models
From the Sigfried and Janet Weis Center for Research (S.F.V., D.E.V.), The Pennsylvania State University College of Medicine, Danville, Pa, and COR Therapeutics, Inc (C.J.H.), South San Francisco, Calif.
Correspondence to Stephen F. Vatner, Charles B. Degenstein Professor, Director of the Henry Hood Research Program, Sigfried and Janet Weis Center for Research, The Pennsylvania State University College of Medicine, 100 N Academy Ave, Danville, PA 17822-2601.
Key Words: receptors, adrenergic • sympathetic nervous system • Gs
overexpression • animal models • heart failure
 |
Introduction |
|---|
Under normal physiological conditions, the heart must be able to increase its output 5-fold to supply the required blood flow to the coronary circulation and skeletal muscles during severe stress. This is normally met by
5-fold increases in myocardial contractility,
3-fold increases in heart rate, and additional increases in stroke
volume.1 This increased load requires a commensurate
increase in myocardial blood flow, because oxygen extraction across the
heart is nearly complete, even under normal conditions. Accordingly,
the design of the cardiovascular system evolved to
conserve myocardial metabolic demand, and consequently
coronary blood flow, at rest, but with considerable reserve
that can be called on rapidly in times of stress. There is a host of
compensatory adjustments, including changes in metabolic
substrates and kinetics, as well as oxygen-carrying capacity, that may
be recruited in response to stress. However, none is more important
than the autonomic nervous system in general, and the sympathetic arm
in particular, in terms of providing large, rapid changes in cardiac
function. When this compensatory mechanism is unavailable, eg, after
treatment with propranolol, the 3-fold increases in heart
rate and 5-fold increases in myocardial contractility
in response to exercise cannot be achieved.1
In this connection, it is recognized that heart failure is a state
characterized by enhanced sympathetic tone, but when the failing
myocardium is challenged by ß-adrenergic stimulation in
vivo or in vitro, the most frequent result is ß-adrenergic
downregulation or desensitization.2 3 4 5 An impairment of
cardiac function leads to autocrine, paracrine, and neurohormonal
adjustments, including a strong
This article has been cited by other articles:
 |
|
 |
|
  U. H. Frey, M. Adamzik, E. Kottenberg-Assenmacher, H. Jakob, I. Manthey, M. Broecker-Preuss, L. Bergmann, G. Heusch, W. Siffert, J. Peters, et al. A novel functional haplotype in the human GNAS gene alters G{alpha}s expression, responsiveness to {beta}-adrenoceptor stimulation, and peri-operative cardiac performance Eur. Heart J., June 1, 2009; 30(11): 1402 - 1410. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H.-Z. Feng, M. Chen, L. S. Weinstein, and J.-P. Jin Removal of the N-terminal Extension of Cardiac Troponin I as a Functional Compensation for Impaired Myocardial {beta}-Adrenergic Signaling J. Biol. Chem., November 28, 2008; 283(48): 33384 - 33393. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Endoh Novel signalling cascade for cardiac hypertrophy activation by uncoupling and internalization of {beta}1-adrenoceptors Cardiovasc Res, April 1, 2008; 78(1): 5 - 7. [Full Text] [PDF]
|
|
|
|
|
|
C. Morisco, C. Marrone, J. Galeotti, D. Shao, D. E. Vatner, S. F. Vatner, and J. Sadoshima Endocytosis machinery is required for {beta}1-adrenergic receptor-induced hypertrophy in neonatal rat cardiac myocytes Cardiovasc Res, April 1, 2008; 78(1): 36 - 44. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. C. Kolwicz, H. Kubo, S. M. MacDonnell, S. R. Houser, and J. R. Libonati Effects of forskolin on inotropic performance and phospholamban phosphorylation in exercise-trained hypertensive myocardium J Appl Physiol, February 1, 2007; 102(2): 628 - 633. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Nishizawa, Y.-T. Shen, F. Rossi, C. Hong, J. Robbins, Y. Ishikawa, J. Sadoshima, D. E. Vatner, and S. F. Vatner Altered autonomic control in conscious transgenic rabbits with overexpressed cardiac Gs{alpha} Am J Physiol Heart Circ Physiol, February 1, 2007; 292(2): H971 - H975. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G.-C. Fan, Q. Yuan, G. Song, Y. Wang, G. Chen, J. Qian, X. Zhou, Y. J. Lee, M. Ashraf, and E. G. Kranias Small Heat-Shock Protein Hsp20 Attenuates {beta}-Agonist-Mediated Cardiac Remodeling Through Apoptosis Signal-Regulating Kinase 1 Circ. Res., November 24, 2006; 99(11): 1233 - 1242. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. D. Faulx, P. Ernsberger, D. Vatner, R. D. Hoffman, W. Lewis, R. Strachan, and B. D. Hoit Strain-dependent {beta}-adrenergic receptor function influences myocardial responses to isoproterenol stimulation in mice Am J Physiol Heart Circ Physiol, July 1, 2005; 289(1): H30 - H36. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. A. Grandy, E. M. Denovan-Wright, G. R. Ferrier, and S. E. Howlett Overexpression of human {beta}2-adrenergic receptors increases gain of excitation-contraction coupling in mouse ventricular myocytes Am J Physiol Heart Circ Physiol, September 1, 2004; 287(3): H1029 - H1038. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Foerster, F. Groner, J. Matthes, W. J. Koch, L. Birnbaumer, and S. Herzig Cardioprotection specific for the G protein Gi2 in chronic adrenergic signaling through {beta}2-adrenoceptors PNAS, November 25, 2003; 100(24): 14475 - 14480. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Okumura, G. Takagi, J.-i. Kawabe, G. Yang, M.-C. Lee, C. Hong, J. Liu, D. E. Vatner, J. Sadoshima, S. F. Vatner, et al. Disruption of type 5 adenylyl cyclase gene preserves cardiac function against pressure overload PNAS, August 19, 2003; 100(17): 9986 - 9990. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F.-L. Tan, C. S. Moravec, J. Li, C. Apperson-Hansen, P. M. McCarthy, J. B. Young, and M. Bond The gene expression fingerprint of human heart failure PNAS, August 20, 2002; 99(17): 11387 - 11392. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. A Nikolaidis, T. Hentosz, A. Doverspike, R. Huerbin, C. Stolarski, Y.-T. Shen, and R. P Shannon Catecholamine stimulation is associated with impaired myocardial O2 utilization in heart failure Cardiovasc Res, February 1, 2002; 53(2): 392 - 404. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Dash, V. J. Kadambi, A. G. Schmidt, N. M. Tepe, D. Biniakiewicz, M. J. Gerst, A. M. Canning, W. T. Abraham, B. D. Hoit, S. B. Liggett, et al. Interactions Between Phospholamban and {{beta}}-Adrenergic Drive May Lead to Cardiomyopathy and Early Mortality Circulation, February 13, 2001; 103(6): 889 - 896. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. J. Lefkowitz and J. T. Willerson Prospects for Cardiovascular Research JAMA, February 7, 2001; 285(5): 581 - 587. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Ukai, C.-P. Cheng, H. Tachibana, A. Igawa, Z.-S. Zhang, H.-J. Cheng, and W. C. Little Allopurinol Enhances the Contractile Response to Dobutamine and Exercise in Dogs With Pacing-Induced Heart Failure Circulation, February 6, 2001; 103(5): 750 - 755. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X.-J. Du, X.-M. Gao, B. Wang, G. L Jennings, E. A Woodcock, and A. M Dart Age-dependent cardiomyopathy and heart failure phenotype in mice overexpressing {beta}2-adrenergic receptors in the heart Cardiovasc Res, December 1, 2000; 48(3): 448 - 454. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X.-F. Deng, D. G. Rokosh, and P. C. Simpson Autonomous and Growth Factor-Induced Hypertrophy in Cultured Neonatal Mouse Cardiac Myocytes : Comparison With Rat Circ. Res., October 27, 2000; 87(9): 781 - 788. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Sabri, E. Pak, S. A. Alcott, B. A. Wilson, and S. F. Steinberg Coupling Function of Endogenous {alpha}1- and {beta}-Adrenergic Receptors in Mouse Cardiomyocytes Circ. Res., May 26, 2000; 86(10): 1047 - 1053. [Abstract] [Full Text] [PDF]
|
|