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European Journal of Heart Failure 2008 10(9):840-849; doi:10.1016/j.ejheart.2008.06.020
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© 2008 European Society of Cardiology

Increased expression of adrenomedullin 2/intermedin in rat hearts with congestive heart failure

Takuo Hirosea,*, Kazuhito Totsunea,b, Nobuyoshi Moric, Ryo Morimotod, Masahiro Hashimotoa, Yukiko Nakashigea, Hirohito Metokia,e, Kei Asayamab, Masahiro Kikuyaa, Takayoshi Ohkubob,f, Junichiro Hashimotob,f, Hironobu Sasanog, Masahiro Kohzukic, Kazuhiro Takahashib,h and Yutaka Imaia,b

a Department of Clinical Pharmacology and Therapeutics, Tohoku University Graduate School of Pharmaceutical Sciences and Medicine 6-3 Aramaki-aza-aoba, Aoba-ku, Sendai 980-8578, Japan
b Tohoku University 21st Center of Excellence Program "Comprehensive Research and Education Center for Planning of Drug Development and Clinical Evaluation" (CRESCENDO) 6-3 Aramaki-aza-aoba, Aoba-ku, Sendai 980-8578, Japan
c Department of Internal Medicine and Rehabilitation Science, Tohoku University School of Medicine 1-1 Seiryo-machi, Aoba-ku, Sendai 980-8574, Japan
d Department of Medicine, Tohoku University School of Medicine 1-1 Seiryo-machi, Aoba-ku, Sendai 980-8574, Japan
e Department of Medical Genetics, Tohoku University School of Medicine 1-1 Seiryo-machi, Aoba-ku, Sendai 980-8574, Japan
f Department of Planning for Drug Development and Clinical Evaluation, Tohoku University Graduate School of Pharmaceutical Sciences and Medicine 2-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan
g Department of Pathology, Tohoku University School of Medicine 1-1 Seiryo-machi, Aoba-ku, Sendai 980-8574, Japan
h Department of Endocrinology and Applied Medical Science, Tohoku University Graduate School of Medicine 2-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan

* Corresponding author. Tel.: +81 22 795 6807; fax: +81 22 795 6839. E-mail address: hirose-t{at}m.tains.tohoku.ac.jp (T. Hirose).


  Abstract

Adrenomedullin 2/intermedin (AM2/IMD) is a novel member of the calcitonin/calcitonin gene-related peptide family. To investigate the pathophysiological role of AM2/IMD in heart failure, we examined the expression of AM2/IMD, adrenomedullin (AM) and receptor complex components (calcitonin receptor-like receptor, three types of receptor activity-modifying proteins) by quantitative RT-PCR and immunohistochemistry in the hearts and kidneys of rats with congestive heart failure (CHF). Significantly increased levels of AM2/IMD mRNAwere found in the atrium, right ventricle, non-infarcted part of the left ventricle and the infarcted part of the left ventricle of CHF rats, compared with sham operated rats (about 2.8-fold, 1.7-fold, 1.7-fold and 2.5-fold, respectively). Expression levels of mRNA encoding AM and the receptor complex components were also increased in the hearts of CHF rats. In a separate experiment, AM2/IMD mRNA levels in the heart did not differ between Wistar—Kyoto and spontaneously hypertensive rats. In both sham operated and CHF rats, the myocardium was diffusely immunostained with AM2/IMD. The fibrotic infarcted layer was not immunostained with AM2/IMD but was surrounded by positively immunostained myocardial layers. These findings suggest that the expression of AM2/IMD is enhanced in the failing heart, and AM2/IMD has a certain pathophysiological role in heart failure.

Key Words: Adrenomedullin • Adrenomedullin 2/Intermedin • Heart failure • RT-PCR • Immunohistochemistry

Received February 7, 2008; Revised April 29, 2008; Accepted June 30, 2008


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