Chronic beta-adrenoceptor blockade prevents the development of beta-adrenergic subsensitivity in experimental right-sided congestive heart failure in dogs.
BACKGROUND
The reductions of myocardial beta-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 beta-receptor blockade.


RESULTS
We administered the oral beta-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 beta-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 beta-receptor or adenylate cyclase activity after nadolol treatment. However, nadolol treatment prevented the reduction of myocardial beta-receptor density and attenuated the decrease in the cardiac beta-adrenergic sensitivity that occurred in right heart failure.


CONCLUSIONS
Excessive sympathetic stimulation may play an important role in the development of beta-receptor downregulation and beta-adrenergic subsensitivity in right heart failure.
Department of Medicine, University of Rochester Medical Center, N.Y. 14642.
C S
CS
Liang
R P
RP
Frantz
M
M
Suematsu
S
S
Sakamoto
J T
JT
Sullebarger
T M
TM
Fan
L
L
Guthinger
D000262:Adenylyl Cyclases / Q000378:metabolism; D000319:Adrenergic beta-Antagonists; D000818:Animals; D001011:Aorta / Q000503:physiopathology; D001794:Blood Pressure / Q000187:drug effects; D004280:Dobutamine / Q000494:pharmacology; D004285:Dogs; D006333:Heart Failure / Q000097:blood / Q000188:drug therapy / Q000503:physiopathology*; D006339:Heart Rate / Q000187:drug effects; D007545:Isoproterenol / Q000494:pharmacology; D009200:Myocardial Contraction; D009206:Myocardium / Q000378:metabolism; D009248:Nadolol / Q000627:therapeutic use*; D009638:Norepinephrine / Q000378:metabolism; D011943:Receptors, Adrenergic, beta / Q000187:drug effects
D000319:Adrenergic beta-Antagonists; D011943:Receptors, Adrenergic, beta; D004280:Dobutamine; D009248:Nadolol; D000262:Adenylyl Cyclases; D007545:Isoproterenol; D009638:Norepinephrine