ABNORMAL BETA-ADRENERGIC TRANSMEMBRANE SIGNALING IN RABBITS WITH ADRIAMYCIN-INDUCED CARDIOMYOPATHY

We investigated alterations in the beta-adrenergic receptor-adenylate cyclase system in rabbits with congestive heart failure induced by adr iamycin cardiotoxicity. A dose of 24 mg/kg adriamycin was administered over 16 weeks in 16 rabbits. Five of them died and 4 of them could no t tolerate the full dose of adriamycin. Complete data were obtained in the remaining 7 rabbits. Another 7 rabbits received physiological sal ine for the same period and served as controls. Plasma norepinephrine concentration increased in adriamycin-treated rabbits, but not in the control rabbits. Cardiac output was lower in the adriamycin-treated gr oup than in the control group. Both the left and right ventricular end -diastolic pressure were higher in the adriamycin-treated group. The d ensity of myocardial beta-adrenergic receptors and the norepinephrine content were reduced in both ventricles in the adriamycin-treated grou p. Basal and isoproterenol-, sodium fluoride- and forskolin-stimulated adenylate cyclase activities were lower in the adriamycin-treated gro up, Thus, alterations in beta-adrenergic signaling occurred in both ve ntricles in animals with chronic biventricular failure induced by adri amycin. These may be the result of post-receptor abnormalities, includ ing abnormalities of guanine nucleotide-binding proteins or of the cat alytic unit of adenylate cyclase.