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.
Uno
Y
Y
2nd Department of Internal Medicine Gifu University School of Medicine, Japan.
Minatoguchi
S
S
Imai
Y
Y
Koshiji
M
M
Kakami
M
M
Yokoyama
H
H
Ito
H
H
Hirakawa
S
S
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