Distinct down-regulation of cardiac beta 1- and beta 2-adrenoceptors in different human heart diseases.

Cardiac beta-adrenoceptor density and beta 1- and beta 2-subtype distribution were examined in human left ventricular myocardium from transplant donors serving as controls and from patients with mitral valve stenosis, aortic valve stenosis, idiopathic dilated cardiomyopathy, and ischaemic cardiomyopathy respectively. The total beta-adrenoceptor density was similar in transplant donors and patients with moderate heart failure (NYHA II-III) due to mitral valve stenosis, but was markedly reduced in all forms of severe heart failure (NYHA III-IV) studied. A reduction of both beta 1- and beta 2-adrenoceptors was found in patients with severe heart failure due to mitral valve stenosis or ischaemic cardiomyopathy. In contrast, a selective down-regulation of beta 1-adrenoceptors with unchanged beta 2-adrenoceptors and hence a relative increase in the latter was observed in idiopathic dilated cardiomyopathy and aortic valve stenosis. It is concluded that the extent of total beta-adrenoceptor down-regulation is related to the degree of heart failure. Selective loss of beta 1-adrenoceptors is not specific for idiopathic dilated cardiomyopathy but also occurs in aortic valve stenosis. Changes in beta 1- and beta 2-subtype distribution are rather related to the aetiology than to the clinical degree of heart failure.