Modulation of noradrenaline release via activation of presynaptic β-adrenoceptors in rabbits with adriamycin-induced cardiomyopathy

Yoshihiro Uno, Shinya Minatoguchi, Yoko Imai, Masatoshi Koshino, Masao Kakami, Hitomi Yokoyama, Hiroyasu Ito, Senri Hirakawa

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6 Citations (Scopus)

Abstract

We investigated the role of β-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 (0.06μg/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 β-adrenoceptors is reduced. This might be due to down-regulation of presynaptic β-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.

Original languageEnglish
Pages (from-to)426-433
Number of pages8
JournalJAPANESE CIRCULATION JOURNAL
Volume57
Issue number5
DOIs
Publication statusPublished - 1993
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Physiology
  • Cardiology and Cardiovascular Medicine

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