Effects of chronic beta-blockade on beta-receptors and adenylate cyclase activity in the canine heart.
To test the hypothesis that beta-receptors 'up-regulate' during chronic beta-blockade, myocardial beta-receptor density, affinity and functional sensitivity were examined in dogs before and after chronic beta-blockade. Membrane preparations from the left ventricle and right atrium were assayed for beta-receptors in 8 control dogs, and 8 dogs given oral nadolol (4 mg/kg) twice a day for 3 weeks. Beta-receptor density and affinity of membrane fractions were determined using 3H-dihydroalprenolol (0.5-20 nM), and Scatchard analysis. Beta-receptor densities after chronic beta-blockade were 419 +/- 28 (mean +/- SEM) and 436 +/- 47 fmol/mg protein in membranes from the left ventricle and right atrium respectively. These values were not significantly different from the left ventricle (412 +/- 25) or the right atrium (413 +/- 25) in control dogs. Beta-receptor affinities were 5.6 +/- 0.5 nM (left ventricle) and 8.5 +/- 1.1 nM (right atrium) after chronic beta-blockade, and not significantly different from control (6.9 +/- 0.7 nM, ventricle; 11.3 +/- 0.9 nM, atrium). Beta-receptor sensitivity was determined in membrane fractions from the left ventricle by analysis of the dose-response relationship between isoproterenol and the formation of c-AMP (pmol/min/mg protein). The concentration of isoproterenol that resulted in 50% of the maximal response was not significantly altered by chronic beta-blockade. Maximally stimulated adenylate cyclase with Gpp(NH)p or NaF was also unchanged by beta-blockade. These results suggest that in the canine heart, chronic beta-blockade does not lead to 'up-regulation' of beta-receptors nor catecholamine supersensitivity.
Becker
D M
DM
Department of Medicine, Loyola University Medical Center, Maywood, Ill.
Romano
F D
FD
Scanlon
P J
PJ
Jones
S B
SB
Euler
D E
DE
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D004285:Dogs; D005260:Female; D006321:Heart / Q000187:drug effects*; D007545:Isoproterenol / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D009206:Myocardium / Q000201:enzymology*; D009248:Nadolol / Q000494:pharmacology*; D011943:Receptors, Adrenergic, beta / Q000032:analysis / Q000187:drug effects / Q000378:metabolism*
D011943:Receptors, Adrenergic, beta; D009248:Nadolol; D000262:Adenylyl Cyclases; D007545:Isoproterenol