Myocardial beta-adrenergic receptor function during the development of pacing-induced heart failure.

The development of pacing-induced heart failure was studied in chronically instrumented, conscious dogs paced at a rate of 240 beats/min for 1 d (n = 6), 1 wk (n = 6), and 3-4 wk (n = 7). Left ventricular (LV) dP/dt was decreased (P < 0.0125) at 1 d, LV end-diastolic pressure and heart rate were increased (P < 0.0125) at 1 wk, but clinical signs of heart failure were only observed after 3-4 wk of pacing. Plasma norepinephrine rose (P < 0.0125) after 1 d of pacing, whereas LV norepinephrine was reduced (P < 0.0125) only after 3-4 wk of pacing. Both the fraction of beta-adrenergic receptors binding agonist with high affinity and adenylyl cyclase activity decreased (P < 0.0125) after 1 d of pacing. Total beta-adrenergic receptor density was not changed at any time point, but beta 1-adrenergic receptor density was decreased (P < 0.0125) after 1 wk. The functional activity of the guanine nucleotide binding protein, Gs, was not reduced, but the Gi alpha 2 isoform of the alpha subunit of the GTP-inhibitory protein rose after 3-4 wk of pacing. Thus, myocardial beta-adrenergic signal transduction undergoes change shortly (1d) after the initiation of pacing, before heart failure develops. The mechanism of beta-adrenergic receptor dysfunction in pacing-induced heart failure is characterized initially by elevated plasma levels of catecholamines, uncoupling of beta-adrenergic receptors, and a defect in the adenylyl cyclase catalytic unit. Selective down-regulation of beta 1-adrenergic receptors, increases in Gi alpha 2, and decreases in myocardial catecholamine levels occur as later events.

[1]  T Ihara,et al.  Alterations in left ventricular diastolic function in conscious dogs with pacing-induced heart failure. , 1992, The Journal of clinical investigation.

[2]  J. Liao,et al.  Specific receptor-guanine nucleotide binding protein interaction mediates the release of endothelium-derived relaxing factor. , 1992, Circulation research.

[3]  W. Schmitz,et al.  Increased messenger RNA level of the inhibitory G protein alpha subunit Gi alpha-2 in human end-stage heart failure. , 1992, Circulation research.

[4]  C M Bloor,et al.  Myocardial,β‐Adrenergic Receptor Expression and Signal Transduction After Chronic Volume‐Overload Hypertrophy and Circulatory Congestion , 1992, Circulation.

[5]  P. Molinoff,et al.  Beta-adrenergic receptor-G protein-adenylate cyclase complex in experimental canine congestive heart failure produced by rapid ventricular pacing. , 1991, Circulation research.

[6]  J. Rouleau,et al.  Dysfunction of the beta- and alpha-adrenergic systems in a model of congestive heart failure. The pacing-overdrive dog. , 1991, Circulation research.

[7]  S. Vatner,et al.  Alterations in myocardial contractility in conscious dogs with dilated cardiomyopathy. , 1991, The American journal of physiology.

[8]  K. Jakobs,et al.  Increase of Gi alpha in human hearts with dilated but not ischemic cardiomyopathy. , 1990, Circulation.

[9]  J. Port,et al.  Beta-adrenergic pathways in nonfailing and failing human ventricular myocardium. , 1990, Circulation.

[10]  Daly Pa,et al.  Myocardial catecholamines and the pathophysiology of heart failure. , 1990 .

[11]  M. Packer,et al.  Role of the sympathetic nervous system in chronic heart failure. A historical and philosophical perspective. , 1990, Circulation.

[12]  N. Heitkamp,et al.  SAS system for elementary statistical analysis , 1990 .

[13]  M. Michel,et al.  Myocardial beta-adrenoceptor changes in heart failure: concomitant reduction in beta 1- and beta 2-adrenoceptor function related to the degree of heart failure in patients with mitral valve disease. , 1989, Journal of the American College of Cardiology.

[14]  J. Saffitz,et al.  Distribution of beta-adrenergic receptors in failing human myocardium. Implications for mechanisms of down-regulation. , 1989, Circulation.

[15]  J. Gordon,et al.  Beta-adrenergic receptor number and adenylate cyclase function in denervated transplanted and cardiomyopathic human hearts. , 1989, Circulation.

[16]  G. Norbiato,et al.  Identification of alpha 1-adrenergic receptors on sarcolemma from normal subjects and patients with idiopathic dilated cardiomyopathy: characteristics and linkage to GTP-binding protein. , 1989, Circulation research.

[17]  W. Baumgartner,et al.  Increase of the 40,000-mol wt pertussis toxin substrate (G protein) in the failing human heart. , 1988, The Journal of clinical investigation.

[18]  C. Liang,et al.  Alterations in cardiac β-adrenoceptor responsiveness and adenylate cyclase system by congestive heart failure in dogs , 1987 .

[19]  M. Creager,et al.  Baroreceptor function in congestive heart failure: effect on neurohumoral activation and regional vascular resistance. , 1987, Circulation.

[20]  M. Bristow,et al.  Assessment of the beta-adrenergic receptor pathway in the intact failing human heart: progressive receptor down-regulation and subsensitivity to agonist response. , 1986, Circulation.

[21]  S. Jamieson,et al.  Beta 1- and beta 2-adrenergic-receptor subpopulations in nonfailing and failing human ventricular myocardium: coupling of both receptor subtypes to muscle contraction and selective beta 1-receptor down-regulation in heart failure. , 1986, Circulation research.

[22]  S. Vatner,et al.  Loss of high affinity cardiac beta adrenergic receptors in dogs with heart failure. , 1985, The Journal of clinical investigation.

[23]  David R. Sibley,et al.  Molecular mechanisms of receptor desensitization using the β-adrenergic receptor-coupled adenylate cyclase system as a model , 1985, Nature.

[24]  A. Spiegel,et al.  The inhibitory adenylate cyclase coupling protein in pseudohypoparathyroidism. , 1985, The Journal of clinical endocrinology and metabolism.

[25]  N. Kantrowitz,et al.  Beta-adrenergic function in heart muscle disease and heart failure. , 1985, Journal of molecular and cellular cardiology.

[26]  J. Cohn,et al.  Plasma norepinephrine as a guide to prognosis in patients with chronic congestive heart failure. , 1984, The New England journal of medicine.

[27]  D. Harrison,et al.  Study of the normal and failing isolated human heart: decreased response of failing heart to isoproterenol. , 1983, American heart journal.

[28]  T. K. Harden,et al.  Agonist-induced desensitization of the beta-adrenergic receptor-linked adenylate cyclase. , 1983, Pharmacological reviews.

[29]  D C Harrison,et al.  Decreased catecholamine sensitivity and beta-adrenergic-receptor density in failing human hearts. , 1982, The New England journal of medicine.

[30]  P. Molinoff,et al.  Quantitative analysis of drug-receptor interactions: II. Determination of the properties of receptor subtypes. , 1981, Life sciences.

[31]  H. R. Besch.  Characterization of [3H](±)Carazolol Binding to β‐Adrenergic Receptors: Application to Study of β‐Adrenergic Receptor Subtypes in Canine Ventricular Myocardium and Lung , 1981, Circulation research.

[32]  R. Taylor,et al.  CARDIAC β‐ADRENORECEPTORS IN THE THYROXINE‐TREATED DOG , 1981 .

[33]  Morris J. Brown,et al.  Chronic heart failure in the guinea pig increases cardiac α1- and β-adrenoceptors , 1980 .

[34]  D Rodbard,et al.  Ligand: a versatile computerized approach for characterization of ligand-binding systems. , 1980, Analytical biochemistry.

[35]  R. Lefkowitz,et al.  A ternary complex model explains the agonist-specific binding properties of the adenylate cyclase-coupled beta-adrenergic receptor. , 1980, The Journal of biological chemistry.

[36]  T. K. Harden,et al.  Catecholamine-specific desensitization of adenylate cyclase. Evidence for a multistep process. , 1980, The Journal of biological chemistry.

[37]  H. Bourne,et al.  Defect of receptor-cyclase coupling protein in psudohypoparathyroidism. , 1980, The New England journal of medicine.

[38]  J. A. Thomas,et al.  Plasma norepinephrine in congestive heart failure. , 1978, The American journal of cardiology.

[39]  J. Peuler,et al.  Simultaneous single isotope radioenzymatic assay of plasma norepinephrine, epinephrine and dopamine. , 1977, Life sciences.

[40]  H. Bourne,et al.  Selection of a variant lymphoma cell deficient in adenylate cyclase. , 1975, Science.

[41]  C. Londos,et al.  A highly sensitive adenylate cyclase assay. , 1974, Analytical biochemistry.

[42]  D L Eckberg,et al.  Defective cardiac parasympathetic control in patients with heart disease. , 1971, The New England journal of medicine.

[43]  E. Braunwald,et al.  Reduction of the Cardiac Response to Postganglionic Sympathetic Nerve Stimulation in Experimental Heart Failure , 1966 .

[44]  E. Braunwald,et al.  Mechanism of Norepinephrine Depletion in Experimental Heart Failure Produced by Aortic Constriction in the Guinea Pig , 1965, Circulation research.

[45]  E. Braunwald,et al.  CATECHOLAMINE EXCRETION AND CARDIAC STORES OF NOREPINEPHRINE IN CONGESTIVE HEART FAILURE. , 1965, The American journal of medicine.

[46]  Oliver H. Lowry,et al.  Protein measurement with the Folin phenol reagent. , 1951, The Journal of biological chemistry.

[47]  S. Vatner,et al.  Beta-receptors and adenylate cyclase: comparison of nonischemic, ischemic, and postmortem tissue. , 1990, The American journal of physiology.

[48]  M. Caron,et al.  Regulation of adenylyl cyclase-coupled beta-adrenergic receptors. , 1988, Annual review of cell biology.

[49]  J. Cohn,et al.  The autonomic nervous system in congestive heart failure. , 1986, Annual review of medicine.

[50]  R. Kahn,et al.  Antisera of designed specificity for subunits of guanine nucleotide-binding regulatory proteins. , 1986, Proceedings of the National Academy of Sciences of the United States of America.

[51]  L. Jones,et al.  Isolation of Canine Cardiac Sarcolemmal Vesicles , 1984 .