TY - JOUR T1 - Abnormality in Plasma Catecholamines and Myocardial Adrenoceptors in Cardiomyopathic BIO 53.58 Syrian Hamsters and Improvement by Metoprolol Treatment JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 1389 LP - 1395 VL - 283 IS - 3 AU - Shizuo Yamada AU - Takashi Ohkura AU - Tooru Yamadera AU - Osamu Ito AU - Ryohei Kimura AU - Yoshihisa Nozawa AU - Shuji Hayashi AU - Hidekazu Miyake Y1 - 1997/12/01 UR - http://jpet.aspetjournals.org/content/283/3/1389.abstract N2 - The catecholaminergic neuronal activity and the densities ofalpha-1 and beta adrenoceptors and angiotensin II receptors were simultaneously determined in BIO 53.58, a model of idiopathic dilated cardiomyopathy, and F1B control hamsters. Further, we examined the effect of repeated p.o. administration of metoprolol on these biochemical parameters. Compared with F1B control hamsters, there was a significant decrease in Bmax of specific binding of both (−)-[125I]iodocyanopindolol and [3H]prazosin with a marked elevation of plasma catecholamine (mainly norepinephrine and epinephrine) concentrations, in BIO 53.58 hamsters at 11 and 18 weeks of age (severe cardiomyopathic stage), but not at 5 weeks of age. On the other hand, theBmax value of myocardial [125I]angiotensin II binding in BIO 53.58 hamsters was almost identical to that in F1B hamsters. These results suggest a development of down-regulation of myocardial beta andalpha-1 adrenoceptors because of an increased catecholaminergic neuronal activity with aging in BIO 53.58 hamsters. Repeated p.o. administration of a relatively low dose (1 mg/kg/day) of metoprolol for 7 weeks in 11-week-old BIO 53.58 hamsters caused a significant increase of myocardial (−)-[125I]iodocyanopindolol binding sites with a marked reduction in plasma catecholamine levels; this indicated a significant recovery to the F1B levels. The improvement of these biochemical parameters by metoprolol treatment was also accompanied by a significant decrease in the fibrosis in the heart in BIO 53.58 hamsters. These data suggest that catecholaminergic neurons and adrenoceptors play a part in the development of heart failure in idiopathic dilated cardiomyopathy. Consequently, the present study may provide a further pharmacological basis for the use ofbeta-1 adrenoceptor antagonists in patients with idiopathic dilated cardiomyopathy. The American Society for Pharmacology and Experimental Therapeutics ER -