Chronic effects of metoprolol on myocardial beta-adrenergic receptors in doxorubicin-induced cardiac damage in rats.
This study was designed to clarify whether chronic administration of metoprolol had any influence on cardiac beta-adrenergic receptors (BAR) in doxorubicin (DOX)-induced cardiac damage. DOX was injected through the tail vein into rats (3 mg/kg/week, n = 22) for 5 weeks. One week after the final injection, the rats were randomly divided into two groups, M (with metoprolol, 10 mg/kg/day subcutaneously, s.c.; n = 11) and D (without metoprolol; n = 11). After 3-week infusion, plasma norepinephrine (NE) levels and BAR density [[125I]iodocyanopindolol (ICYP) binding on crude membranes] were measured. Left and right ventricular end-diastolic pressure (LVEDP, RVEDP) and myocardial NE levels were also measured, and the results were compared with those from an age-matched control group (C n = 11). Decreased BAR density and increased plasma NE levels were evident in group D, indicating downregulation. In group M, BAR density and plasma NE levels were similar to those in group C. The myocardial NE levels were decreased in group D, but were higher in group M than in group D. The LVEDP and RVEDP were increased in group D, but were almost normal in group M. These results suggest that metoprolol is a promising drug for treatment of DOX-induced cardiac damage.
Fujita
N
N
Department of Cardiology, Tokyo Women's Medical College, Japan.
Hiroe
M
M
Ohta
Y
Y
Horie
T
T
Hosoda
S
S
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D004317:Doxorubicin / Q000633:toxicity*; D006331:Heart Diseases / Q000139:chemically induced / Q000503:physiopathology*; D006439:Hemodynamics / Q000187:drug effects; D066298:In Vitro Techniques; D020120:Iodocyanopindolol; D007700:Kinetics; D008297:Male; D008790:Metoprolol / Q000494:pharmacology*; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D009638:Norepinephrine / Q000097:blood / Q000378:metabolism; D010869:Pindolol / Q000031:analogs & derivatives; D011869:Radioligand Assay; D051381:Rats; D011919:Rats, Inbred Strains; D011943:Receptors, Adrenergic, beta / Q000187:drug effects*
D011943:Receptors, Adrenergic, beta; D004317:Doxorubicin; D020120:Iodocyanopindolol; D010869:Pindolol; D008790:Metoprolol; D009638:Norepinephrine