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

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Abstract
Cardiac β-adrenoceptor density and β1- and β2-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 β-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 β1- and β2-adrenoceptors was found in patients with severe heart failure due to mitral valve stenosis or ischaemic cardiomyopathy. In contrast, a selective down-regulation of β1-adrenoceptors with unchanged β2-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 β-adrenoceptor down-regulation is related to the degree of heart failure. Selective loss of β1-adrenoceptors is not specific for idiopathic dilated cardiomyopathy but also occurs in aortic valve stenosis. Changes in β1- and β2-subtype distribution are rather related to the aetiology than to the clinical degree of heart failure.

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