Abnormal β-adrenergic transmembrane signaling in rabbits with adriamycin-induced cardiomyopathy

Keiichi Nagami, Tsutomu Yoshikawa, Masahiro Suzuki, Yumiko Wainai, Toshihisa Anzai, Shunnosuke Handa

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

We investigated alterations in the β-adrenergic receptor-adenylate cyclase system in rabbits with congestive heart failure induced by adriamycin 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 not tolerate the full dose of adriamycin. Complete data were obtained in the remaining 7 rabbits. Another 7 rabbits received physiological saline 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 group than in the control group. Both the left and right ventricular end-diastolic pressure were higher in the adriamycin-treated group. The density of myocardial β-adrenergic receptors and the norepinephrine content were reduced in both ventricles in the adriamycin-treated group. Basal and isoproterenol-, sodium fluoride- and forskolin-stimulated adenylate cyclase activities were lower in the adriamycin-treated group. Thus, alterations in β-adrenergic signaling occurred in both ventricles in animals with chronic biventricular failure induced by adriamycin. These may be the result of post-receptor abnormalities, including abnormalities of guanine nucleotide-binding proteins or of the catalytic unit of adenylate cyclase.

Original languageEnglish
Pages (from-to)249-255
Number of pages7
JournalJAPANESE CIRCULATION JOURNAL
Volume61
Issue number3
DOIs
Publication statusPublished - 1997 Apr 26

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Keywords

  • Adenylate cyclase
  • Adriamycin-induced cardiomyopathy
  • Congestive heart failure
  • Guanine nucleotide-binding protein
  • β-Adrenergic receptor

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

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