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 sympathetic nerve endings in noradrenaline release in rabbits with cardiomyopathic 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 intravenous administration of adrenaline (0.06 micrograms/kg/min) in adriamycin-treated 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 conditions, adrenaline increased plasma noradrenaline levels in vehicle-treated rabbits. However, in the adriamycin-treated rabbits, adrenaline had no effect on the plasma noradrenaline level. Pretreatment with propranolol (0.2 mg/kg, bolus I.V. + 0.1 mg/kg/hr, continuous infusion) almost completely abolished the rise in plasma noradrenaline associated with adrenaline infusion in vehicle-treated rabbits. These results suggest that in rabbits with adriamycin-induced cardiomyopathy, the noradrenaline release from the sympathetic nerve endings via the activation of presynaptic beta-adrenoceptors is reduced. This might be due to down-regulation of presynaptic beta-adrenoceptors caused by the elevated plasma noradrenaline due to cardiac failure. However, other possibilities such as reduced affinity or impaired signal transduction cannot be excluded.
2nd Department of Internal Medicine Gifu University School of Medicine, Japan.
Y
Y
Uno
S
S
Minatoguchi
Y
Y
Imai
M
M
Koshiji
M
M
Kakami
H
H
Yokoyama
H
H
Ito
S
S
Hirakawa
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D009202:Cardiomyopathies / Q000139:chemically induced / Q000473:pathology*; D004317:Doxorubicin / Q000494:pharmacology; D004837:Epinephrine / Q000008:administration & dosage / Q000097:blood; D006321:Heart / Q000033:anatomy & histology; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D007262:Infusions, Intravenous; D008297:Male; D009411:Nerve Endings / Q000648:ultrastructure; D009638:Norepinephrine / Q000097:blood / Q000378:metabolism*; D009929:Organ Size / Q000187:drug effects; D011292:Premedication; D011433:Propranolol / Q000627:therapeutic use; D011817:Rabbits; D011943:Receptors, Adrenergic, beta / Q000502:physiology*; D017981:Receptors, Neurotransmitter / Q000502:physiology*; D013564:Sympathetic Nervous System / Q000648:ultrastructure
D011943:Receptors, Adrenergic, beta; D017981:Receptors, Neurotransmitter; D004317:Doxorubicin; D011433:Propranolol; D009638:Norepinephrine; D004837:Epinephrine