A sustained increase in β-adrenoceptors during long-term therapy with metoprolol and bisoprolol in patients with heart failure from idiopathic dilated cardiomyopathy

Abstract

Effects of long-term therapy with β 1-selective antagonists (metoprolol, bisoprolol) on β-adrenoceptors in lymphocytes of patients with idiopathic dilated cardiomyopathy (DCM) were examined. There was a significant reduction in the number of lymphocyte β-adrenoceptors in patients with DCM compared to that in healthy volunteers, as demonstrated by a selective decrease in maximum number of binding sites (Bmax) for (−)-[ 125I]iodocyanopindolol (CYP). A therapy with metoprolol and bisoprolol in these patients caused a marked increase in lymphocyte β-adrenoceptor density. The significant increase was observed from 2 or 3 months after the start of therapy with these drugs, and it was maintained during the therapy for 24 months. The left ventricular ejection fraction in patients with DCM was improved by the long-term therapy with metoprolol and bisoprolol, and this effect seems to be correlated with an observed enhancement of lymphocyte β-adrenoceptors in the time course. Also, the increase in lymphocyte β-adrenoceptors appears to be correlated with a gradual amelioration in circulating catecholamine levels by the long-term therapy with β-adrenoceptor antagonists in patients with DCM. Thus, the present study suggests that β-adrenoceptors in lymphocytes of patients with DCM are up-regulated by a long-term therapy with metoprolol and bisoprolol.