Drug- and disease-induced changes of human cardiac beta 1- and beta 2-adrenoceptors.
Cardiac beta-adrenoceptor density and subtype distribution has been determined in different kinds of heart failure. A decrease in cardiac beta-adrenoceptor function appears to be a general phenomenon in all kinds of heart failure. However, cardiac beta 1- and beta 2-adrenoceptors seem to be differentially affected in different kinds of heart failure: while in end-stage idiopathic dilated cardiomyopathy the diminished cardiac beta-adrenoceptor function is due to a selective loss in beta 1-adrenoceptors, in mitral valve disease, tetralogy of Fallot and end-stage ischaemic cardiomyopathy it is characterized by a concomitant reduction in beta 1- and beta 2-adrenoceptors. Chronic treatment of heart failure patients with beta-adrenoceptor antagonists leads to an up-regulation of cardiac beta-adrenoceptors, but in a subtype-selective fashion: beta 1-selective antagonists increase only cardiac beta 1-adrenoceptors, whereas non-selective antagonists increase both beta 1- and beta 2-adrenoceptors. Such a (subtype-selective) 'recovery' of cardiac beta-adrenoceptors may be one reason for the beneficial effects of low-dose beta-adrenoceptor antagonist treatment in patients with severe heart failure.
Brodde
O E
OE
Biochem. Forschungslabor, Universität Essen, F.R.G.
Zerkowski
H R
HR
Borst
H G
HG
Maier
W
W
Michel
M C
MC
D000293:Adolescent; D000328:Adult; D002311:Cardiomyopathy, Dilated / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D003327:Coronary Disease / Q000378:metabolism; D006333:Heart Failure / Q000378:metabolism*; D006801:Humans; D007223:Infant; D007545:Isoproterenol / Q000494:pharmacology; D008790:Metoprolol / Q000494:pharmacology; D008946:Mitral Valve Stenosis / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism*; D011433:Propranolol / Q000494:pharmacology; D011943:Receptors, Adrenergic, beta / Q000032:analysis / Q000187:drug effects*; D013015:Sotalol / Q000494:pharmacology; D013771:Tetralogy of Fallot / Q000378:metabolism
D011943:Receptors, Adrenergic, beta; D011433:Propranolol; D013015:Sotalol; D008790:Metoprolol; D007545:Isoproterenol