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Cardiovascular Research 2001 49(4):721-730; doi:10.1016/S0008-6363(00)00291-1
© 2001 by European Society of Cardiology
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Copyright © 2001, European Society of Cardiology

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

Yoshio Tomodaa,b, Katsuro Kikumotoa, Yoshitaka Isumia, Takeshi Katafuchia, Akira Tanakac, Kenji Kangawaa, Kazuhiro Dohib and Naoto Minaminoa,*

aNational Cardiovascular Center Research Institute, 5-7-1 Fujishirodai, Suita, Osaka 565-8565, Japan
bFirst Department of Internal Medicine, Nara Medical University, Kashihara, Nara 634-0813, Japan
cDepartment of Pathology, Jichi Medical School, Kawachi, Tochigi 329-0498, Japan

* Corresponding author. Tel.: +81-6-6833-5012; fax: +81-6-6872-7485 minamino{at}ri.ncvc.go.jp

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-{alpha} 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.

KEYWORDS Cytokines; Endothelins; Myocytes; Nitric oxide


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