MODULATION OF NORADRENALINE RELEASE VIA ACTIVATION OF PRESYNAPTIC BETA-ADRENOCEPTORS IN RABBITS WITH ADRIAMYCIN-INDUCED CARDIOMYOPATHY

We investigated the role of beta-adrenoceptors at postganglionic sympa thetic nerve endings in noradrenaline release in rabbits with cardiomy opathic congestive heart failure produced by adriamycin (1 mg/kg, I.V. , twice a week for 8 weeks). Plasma noradrenaline levels were measured before, 30 min after, and 60 min after the start of continuous intrav enous administration of adrenaline (0.06 mug/kg/min) in adriamycin-tre ated and vehicle-treated rabbits in anesthetized condition and pithed condition with electrically stimulated sympathetic outflow (3 Hz, 1 ms square wave pulse, 90 V). In both the anesthetized and pithed conditi ons, adrenaline increased plasma noradrenaline levels in vehicle-treat ed rabbits. However, in the adriamycin-treated rabbits, adrenaline had no effect on the plasma noradrenaline level. Pretreatment with propra nolol (0.2 mg/kg, bolus I.V. + 0. 1 mg/kg/hr, continuous infusion) alm ost completely abolished the rise in plasma noradrenaline associated w ith adrenaline infusion in vehicle-treated rabbits. These results sugg est that in rabbits with adriamycin-induced cardiomyopathy, the noradr enaline release from the sympathetic nerve endings via the activation of presynaptic beta-adrenoceptors is reduced. This might be due to dow n-regulation of presynaptic beta-adrenoceptors caused by the elevated plasma noradrenaline due to cardiac failure. However, other possibilit ies such as reduced affinity or impaired signal transduction cannot be excluded.