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.