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

Chang Seng Liang, Robert P. Frantz, Masakuni Suematsu, Susumu Sakamoto, J. Thompson Sullebarger, Tai Hwang M. Fan, Lisa Guthinger

Research output: Contribution to journalArticlepeer-review

23 Scopus citations

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
StatePublished - 1991

Keywords

  • Adenylate cyclase activity
  • Congestive heart failure
  • Nadolol
  • β-adrenergic receptor blockers
  • β-adrenergic receptor density

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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