Cardiac fibroblasts are major production and target cells of adrenomedullin in the heart in vitro

Yoshio Tomoda, Katsuro Kikumoto, Yoshitaka Isumi, Takeshi Katafuchi, Akira Tanaka, Kenji Kangawa, Kazuhiro Dohi, Naoto Minamino

Research output: Contribution to journalArticlepeer-review

57 Scopus citations


Objective: Adrenomedullin (AM) is a potent vasodilator peptide. Plasma AM concentration is increased in patients with various heart diseases, and both myocytes (MCs) and non-myocytes (NMCs) secrete AM and express its receptors. These facts suggest that cardiac cells possess an autocrine/paracrine capability mediated by AM. Methods: MCs and NMCs were prepared from cardiac ventricles of neonatal rats. AM and endothelin-1 concentrations were measured by radioimmunoassays, and interleukin-6 level by a specific bioassay. Total nitrite/nitrate contents were measured with a fluorescence assay kit. Results: A basal secretion rate of AM from NMCs was 2.8-fold higher than that from MCs. Interleukin-1β, tumor necrosis factor-α and lipopolysaccharide stimulated AM secretion from NMCs but not from MCs. AM stimulated interleukin-6 production in the presence of these cytokines or lipopolysaccharide, which was more prominent in NMCs. In the presence of interleukin-1β, AM augmented nitric oxide synthesis 2.7-fold in NMCs, but slightly in MCs. NMCs secreted endothelin-1 at a rate nine times higher than MCs, and AM inhibited endothelin-1 secretion from NMCs. Conclusion: This in vitro study suggests that AM in the heart is mainly produced in NMCs and exerts its effects through NMCs, especially under inflammatory conditions.

Original languageEnglish (US)
Pages (from-to)721-730
Number of pages10
JournalCardiovascular Research
Issue number4
StatePublished - 2001


  • Cytokines
  • Endothelins
  • Myocytes
  • Nitric oxide

ASJC Scopus subject areas

  • Medicine(all)


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