Regional distribution of beta 1- and beta 2-adrenoceptors in the failing and nonfailing human heart.
Total beta-adrenoceptor density and beta 1- and beta 2-subtype distribution in right and left atria and in different ventricular regions from 14 failing and seven nonfailing human hearts have been compared. End-stage heart failure was due to idiopathic dilated cardiomyopathy (n = 8) or ischaemic cardiomyopathy (n = 6). In nonfailing hearts the total beta-adrenoceptor density was similar in the right and left atria and in all the ventricular regions studied (about 70 to 80 fmol/mg protein). The beta 1:beta 2-adrenoceptor ratio in both nonfailing atria was similar (about 70:30%) and was significantly smaller than in the different regions of both ventricles (about 80:20%). The beta 1-subtype density was similar in nonfailing atria and ventricles (about 55 fmol/mg protein). The beta 2-subtype density was significantly higher in the right and left atrium (about 25 fmol/mg protein) than in both ventricles (about 15 fmol/mg protein). In patients with end-stage heart failure due to idiopathic dilated cardiomyopathy or ischaemic cardiomyopathy the total beta-adrenoceptor density was reduced by 50-60% in all regions. On the other hand, the beta 1- and beta 2-subtype distribution differed with the cause of heart failure. In patients with idiopathic dilated cardiomyopathy, the beta 1-adrenoceptor density was not significantly reduced. In patients with ischaemic cardiomyopathy both beta 1- and beta 2-adrenoceptors were reduced in all regions. It is concluded that downregulation of beta-adrenoceptors in patients with end-stage idiopathic dilated cardiomyopathy or ischaemic cardiomyopathy occurs uniformly throughout the heart. The results support the hypothesis that changes in beta-adrenoceptor subtypes may be related to the cause of heart failure.
Steinfath
M
M
Abteilung Allgemeine Pharmakologie, Universitäts-Krankenhaus Eppendorf, Universität Hamburg, FRG.
Lavicky
J
J
Schmitz
W
W
Scholz
H
H
Döring
V
V
Kalmár
P
P
D000328:Adult; D002311:Cardiomyopathy, Dilated / Q000378:metabolism*; D003327:Coronary Disease / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000737:chemistry*; D011869:Radioligand Assay; D011943:Receptors, Adrenergic, beta / Q000032:analysis* / Q000145:classification
D011943:Receptors, Adrenergic, beta