A sustained increase in beta-adrenoceptors during long-term therapy with metoprolol and bisoprolol in patients with heart failure from idiopathic dilated cardiomyopathy.
Effects of long-term therapy with beta 1-selective antagonists (metoprolol, bisoprolol) on beta-adrenoceptors in lymphocytes of patients with idiopathic dilated cardiomyopathy (DCM) were examined. There was a significant reduction in the number of lymphocyte beta-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 beta-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 beta-adrenoceptors in the time course. Also, the increase in lymphocyte beta-adrenoceptors appears to be correlated with a gradual amelioration in circulating catecholamine levels by the long-term therapy with beta-adrenoceptor antagonists in patients with DCM. Thus, the present study suggests that beta-adrenoceptors in lymphocytes of patients with DCM are up-regulated by a long-term therapy with metoprolol and bisoprolol.
Yamada
S
S
Department of Biopharmacy, School of Pharmaceutical Sciences, University of Shizuoka, Japan.
Ohkura
T
T
Uchida
S
S
Inabe
K
K
Iwatani
Y
Y
Kimura
R
R
Hoshino
T
T
Kaburagi
T
T
D058672:Adrenergic beta-2 Receptor Antagonists; D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D017298:Bisoprolol / Q000627:therapeutic use*; D002311:Cardiomyopathy, Dilated / Q000188:drug therapy* / Q000503:physiopathology; D006334:Heart Function Tests; D006801:Humans; D007457:Iodine Radioisotopes; D008790:Metoprolol / Q000627:therapeutic use*; D008875:Middle Aged; D011869:Radioligand Assay; D018343:Receptors, Adrenergic, beta-2 / Q000378:metabolism*; D013237:Stereoisomerism
D058672:Adrenergic beta-2 Receptor Antagonists; D000319:Adrenergic beta-Antagonists; D007457:Iodine Radioisotopes; D018343:Receptors, Adrenergic, beta-2; D008790:Metoprolol; D017298:Bisoprolol