Chronic β-adrenoceptor blockade prevents the development of β-adrenergic subsensitivity in experimental right-sided congestive heart failure in dogs

C. S. Liang, R. P. Frantz, M. Suematsu, S. Sakamoto, J. T. Sullebarger, Tai-Hwang Fan, L. Guthinger

Research output: Contribution to journalArticle

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Abstract

Background. The reductions of myocardial β-adrenergic receptor density and responsiveness to catecholamines in congestive heart failure are associated with excessive sympathetic stimulation. The purpose of this study was to determine whether the myocardial changes could be prevented by β-receptor blockade. Methods and Results. We administered the oral β-receptor blocking agent nadolol (40 mg/day) to dogs during an early stage of experimental right heart failure and to sham-operated dogs for 5 weeks. Animals receiving no nadolol were studied concurrently. Nadolol treatment did not prevent right ventricular hypertrophy or elevated concentrations of plasma norepinephrine that occurred in right heart failure, nor did it affect the decrease in myocardial norepinephrine content and norepinephrine uptake activity, suggesting that the hemodynamic stress imposed on the right ventricle of dogs with right heart failure was similar regardless of the presence or absence of β-receptor blockade. Resting heart rate, right atrial pressure, aortic pressure, cardiac output, right ventricular dP/dt, and left ventricular dP/dt and dP/dt/P measured 5 days after discontinuation of nadolol did not differ significantly from those without nadolol treatment in either right heart failure or sham-operated animals. Sham-operated dogs also showed no changes in myocardial β-receptor or adenylate cyclase activity after nadolol treatment. However, nadolol treatment prevented the reduction of myocardial β-receptor density and attenuated the decrease in the cardiac β-adrenergic sensitivity that occurred in right heart failure. Conclusions. Excessive sympathetic stimulation may play an important role in the development of β-receptor downregulation and β-adrenergic subsensitivity in right heart failure.

Original languageEnglish (US)
Pages (from-to)254-266
Number of pages13
JournalCirculation
Volume84
Issue number1
DOIs
StatePublished - Jan 1 1991

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Nadolol
Adrenergic Agents
Adrenergic Receptors
Heart Failure
Dogs
Norepinephrine
Right Ventricular Hypertrophy
Atrial Pressure
Adenylyl Cyclases
Cardiac Output
Heart Ventricles
Catecholamines
Arterial Pressure
Down-Regulation
Heart Rate
Hemodynamics

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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Chronic β-adrenoceptor blockade prevents the development of β-adrenergic subsensitivity in experimental right-sided congestive heart failure in dogs. / Liang, C. S.; Frantz, R. P.; Suematsu, M.; Sakamoto, S.; Sullebarger, J. T.; Fan, Tai-Hwang; Guthinger, L.

In: Circulation, Vol. 84, No. 1, 01.01.1991, p. 254-266.

Research output: Contribution to journalArticle

Liang, C. S. ; Frantz, R. P. ; Suematsu, M. ; Sakamoto, S. ; Sullebarger, J. T. ; Fan, Tai-Hwang ; Guthinger, L. / Chronic β-adrenoceptor blockade prevents the development of β-adrenergic subsensitivity in experimental right-sided congestive heart failure in dogs. In: Circulation. 1991 ; Vol. 84, No. 1. pp. 254-266.
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N2 - Background. The reductions of myocardial β-adrenergic receptor density and responsiveness to catecholamines in congestive heart failure are associated with excessive sympathetic stimulation. The purpose of this study was to determine whether the myocardial changes could be prevented by β-receptor blockade. Methods and Results. We administered the oral β-receptor blocking agent nadolol (40 mg/day) to dogs during an early stage of experimental right heart failure and to sham-operated dogs for 5 weeks. Animals receiving no nadolol were studied concurrently. Nadolol treatment did not prevent right ventricular hypertrophy or elevated concentrations of plasma norepinephrine that occurred in right heart failure, nor did it affect the decrease in myocardial norepinephrine content and norepinephrine uptake activity, suggesting that the hemodynamic stress imposed on the right ventricle of dogs with right heart failure was similar regardless of the presence or absence of β-receptor blockade. Resting heart rate, right atrial pressure, aortic pressure, cardiac output, right ventricular dP/dt, and left ventricular dP/dt and dP/dt/P measured 5 days after discontinuation of nadolol did not differ significantly from those without nadolol treatment in either right heart failure or sham-operated animals. Sham-operated dogs also showed no changes in myocardial β-receptor or adenylate cyclase activity after nadolol treatment. However, nadolol treatment prevented the reduction of myocardial β-receptor density and attenuated the decrease in the cardiac β-adrenergic sensitivity that occurred in right heart failure. Conclusions. Excessive sympathetic stimulation may play an important role in the development of β-receptor downregulation and β-adrenergic subsensitivity in right heart failure.

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