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

doi:10.1016/S0008-6363(00)00291-1

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

Pharmacology

Research output: Contribution to journal › Article › peer-review

57 Scopus citations

Abstract

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 language	English (US)
Pages (from-to)	721-730
Number of pages	10
Journal	Cardiovascular Research
Volume	49
Issue number	4
DOIs	https://doi.org/10.1016/S0008-6363(00)00291-1
State	Published - 2001

Keywords

Cytokines
Endothelins
Myocytes
Nitric oxide

ASJC Scopus subject areas

Medicine(all)

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10.1016/S0008-6363(00)00291-1

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@article{a4e06d531b8146d29f157702cfd3ff24,

title = "Cardiac fibroblasts are major production and target cells of adrenomedullin in the heart in vitro",

abstract = "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.",

keywords = "Cytokines, Endothelins, Myocytes, Nitric oxide",

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

note = "Funding Information: The authors are grateful to Dr K. Kitamura and Professor T. Eto of Miyazaki Medical College, T. Tsuji of Shionogi & Co. Ltd., Professor K. Yoshizaki and Dr N. Nishimoto of Osaka University, Professor K. Nakao and Dr Y. Saito of Kyoto University, for donation of antisera against AM and cAMP, monoclonal antibody against AM, MH60.BSF-2 cells, antiserum against ET-1 and preparation technique of MCs and NMCs. The authors thank M. Nakatani and M. Higuchi of this institute for technical assistance. This work was supported in part by the Special Coordination Fund for the Promotion of Science and Technology from the Science and Technology Agency, by the research grants from the Ministry of Education, Science and Culture, the Ministry of Health and Welfare, and the Health Sciences Foundation of Japan.",

year = "2001",

doi = "10.1016/S0008-6363(00)00291-1",

language = "English (US)",

volume = "49",

pages = "721--730",

journal = "Cardiovascular Research",

issn = "0008-6363",

publisher = "Oxford University Press",

number = "4",

}

TY - JOUR

T1 - Cardiac fibroblasts are major production and target cells of adrenomedullin in the heart in vitro

AU - Tomoda, Yoshio

AU - Kikumoto, Katsuro

AU - Isumi, Yoshitaka

AU - Katafuchi, Takeshi

AU - Tanaka, Akira

AU - Kangawa, Kenji

AU - Dohi, Kazuhiro

AU - Minamino, Naoto

N1 - Funding Information: The authors are grateful to Dr K. Kitamura and Professor T. Eto of Miyazaki Medical College, T. Tsuji of Shionogi & Co. Ltd., Professor K. Yoshizaki and Dr N. Nishimoto of Osaka University, Professor K. Nakao and Dr Y. Saito of Kyoto University, for donation of antisera against AM and cAMP, monoclonal antibody against AM, MH60.BSF-2 cells, antiserum against ET-1 and preparation technique of MCs and NMCs. The authors thank M. Nakatani and M. Higuchi of this institute for technical assistance. This work was supported in part by the Special Coordination Fund for the Promotion of Science and Technology from the Science and Technology Agency, by the research grants from the Ministry of Education, Science and Culture, the Ministry of Health and Welfare, and the Health Sciences Foundation of Japan.

PY - 2001

Y1 - 2001

N2 - 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.

AB - 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.

KW - Cytokines

KW - Endothelins

KW - Myocytes

KW - Nitric oxide

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U2 - 10.1016/S0008-6363(00)00291-1

DO - 10.1016/S0008-6363(00)00291-1

M3 - Article

C2 - 11230971

AN - SCOPUS:0035113290

SN - 0008-6363

VL - 49

SP - 721

EP - 730

JO - Cardiovascular Research

JF - Cardiovascular Research

IS - 4

ER -

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

Abstract

Keywords

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