Spare receptors for beta-adrenoceptor-mediated positive inotropic effects of catecholamines in the human heart.
We studied whether the human heart has spare receptors for beta-adrenoceptor-mediated positive inotropic effects. Thus, we assessed in right atria and left papillary muscles of patients with different degrees of heart failure under identical experimental conditions affinity (pKI values from (-)-[125I]iodocyanopindolol binding) and potency (pD2 values from contractile responses) for isoprenaline, adrenaline, and noradrenaline in comparison with rat heart. Plots of beta-adrenoceptor occupancy versus responses constructed from these data revealed that rat left atria and papillary muscles had a large receptor reserve for all three beta-adrenoceptor agonists: 50% of maximal response was produced with only 1-3% of beta-adrenoceptor occupancy. In human heart, however, receptor reserve was considerably lower: 50% of maximal response required 8-10% (in right atria) and 20-25% (in left papillary muscles) occupation of beta-adrenoceptors. Receptor reserve declined further with an increasing degree of heart failure (and decreasing beta-adrenoceptor number): in end-stage heart failure (New York Heart Association class IV) both in right atria and left papillary muscles a 1:1 ratio between beta-adrenoceptor occupancy and responses was observed. These data show that the human heart has only a small receptor reserve for beta-adrenoceptor agonists. This may explain why a decrease in beta-adrenoceptor number leads to a decrease in beta-adrenoceptor function early in the development of heart failure.
Brown
L
L
Department of Internal Medicine, University of Essen, F.R.G.
Deighton
N M
NM
Bals
S
S
Söhlmann
W
W
Zerkowski
H R
HR
Michel
M C
MC
Brodde
O E
OE
D000262:Adenylyl Cyclases / Q000032:analysis; D000328:Adult; D000368:Aged; D000818:Animals; D002395:Catecholamines / Q000032:analysis*; D005260:Female; D006333:Heart Failure / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D009200:Myocardial Contraction / Q000187:drug effects*; D009206:Myocardium / Q000737:chemistry*; D051381:Rats; D011943:Receptors, Adrenergic, beta / Q000032:analysis*; D013268:Stimulation, Chemical
D002395:Catecholamines; D011943:Receptors, Adrenergic, beta; D000262:Adenylyl Cyclases