ABNORMALITY IN PLASMA-CATECHOLAMINES AND MYOCARDIAL ADRENOCEPTORS IN CARDIOMYOPATHIC BIO-53.58 SYRIAN-HAMSTERS AND IMPROVEMENT BY METOPROLOL TREATMENT

The catecholaminergic neuronal activity and the densities of alpha-i a nd 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 repeate d p.o. administration of metoprolol on these biochemical parameters. C ompared with F1B control hamsters, there was a significant decrease in B-max of specific binding of both (-)-[I-125]iodocyanopindolol and [H -3]prazosin with a marked elevation of plasma catecholamine (mainly no repinephrine and epinephrine) concentrations, in BIO 53.58 hamsters at Ii and 18 weeks of age (severe cardiomyopathic stage), but not at 5 w eeks of age. On the other hand, the B-max value of myocardial [I-125]a ngiotensin II binding in BIO 53.58 hamsters was almost identical to th at in F1B hamsters. These results suggest a development of down-regula tion of myocardial beta and alpha-i adrenoceptors because of an increa sed catecholaminergic neuronal activity with aging in BIO 53.58 hamste rs. Repeated p.o. administration of a relatively low dose (1 mg/kg/day ) of metoprolol for 7 weeks in Ii-week-old BIO 53.58 hamsters caused a significant increase of myocardial (-)-[I-125]iodocyanopindolol bindi ng 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 accompa nied by a significant decrease in the fibrosis in the heart in BIO 53. 58 hamsters. These data suggest that catecholaminergic neurons and adr enoceptors play a part in the development of heart failure in idiopath ic dilated cardiomyopathy. Consequently, the present study may provide a further pharmacological basis for the use of beta-1 adrenoceptor an tagonists in patients with idiopathic dilated cardiomyopathy.