Down-regulated beta-adrenoceptors in severely failing human ventricles: uniform regional distribution, but no increased internalization.
In chronic heart failure cardiac beta-adrenoceptors are decreased. In this study we investigated whether a) in severely failing human ventricles beta-adrenoceptors are uniformly decreased or regional variations exist, and b) the beta-adrenoceptor decrease is caused by increased internalization or is a real loss in beta-adrenoceptors. For this purpose we assessed beta-adrenoceptor number and subtype distribution in a particulate fraction (mainly sarcolemmal plasma membranes) and a light vesicle fraction of right and left ventricular segments (obtained by cutting transversal rings of 2 cm from the midventricular regions) of explanted hearts from 2 patients with end-stage congestive dilated cardiomyopathy (DCM) and one patient with end-stage ischemic cardiomyopathy (ICM). In all three hearts ventricular beta-adrenoceptor number was very low (7.5-10 and 21-26 fmol/mg protein in DCM, 15-22 fmol/mg protein in ICM compared to 68-74 fmol/mg protein in non-failing ventricles). beta-Adrenoceptors were uniformly decreased over the whole ventricular region and no considerable regional variations existed. The same held true for beta 1- and beta 2-adrenoceptors. In ICM decrease in beta-adrenoceptors was due to a concomitant reduction in beta 1- and beta 2-adrenoceptors, in DCM it was mainly caused by beta 1-adrenoceptor down-regulation. In all ventricular segments investigated light vesicle beta-adrenoceptors amounted to about 5-7% of total ventricular beta-adrenoceptors, and this was not significantly different from non-failing left ventricles. We conclude that a) in severely failing human ventricles beta-adrenoceptors are evenly down-regulated and no regional variations exist, and b) the decrease in beta-adrenoceptors is not due to enhanced internalization but is a real loss of beta-adrenoceptors.
Pitschner
H F
HF
Kerckhoff-Klinik, Bad Nauheim, FRG.
Droege
A
A
Mitze
M
M
Schlepper
M
M
Brodde
O E
OE
D000328:Adult; D002311:Cardiomyopathy, Dilated / Q000503:physiopathology*; D002462:Cell Membrane / Q000737:chemistry; D002908:Chronic Disease; D015536:Down-Regulation; D005260:Female; D006352:Heart Ventricles; D006801:Humans; D008297:Male; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000503:physiopathology*; D011943:Receptors, Adrenergic, beta / Q000032:analysis / Q000502:physiology*; D012508:Sarcolemma / Q000737:chemistry
D011943:Receptors, Adrenergic, beta