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

Takuo Hirose, Kazuhito Totsune, Nobuyoshi Mori, Ryo Morimoto, Masahiro Hashimoto, Yukiko Nakashige, Hirohito Metoki, Kei Asayama, Masahiro Kikuya, Takayoshi Ohkubo, Junichiro Hashimoto, Hironobu Sasano, Masahiro Kohzuki, Kazuhiro Takahashi, Yutaka Imai

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37 Citations (Scopus)


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 mRNA were 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.

Original languageEnglish
Pages (from-to)840-849
Number of pages10
JournalEuropean Journal of Heart Failure
Issue number9
Publication statusPublished - 2008 Sept


  • Adrenomedullin
  • Adrenomedullin 2/Intermedin
  • Heart failure
  • Immunohistochemistry
  • RT-PCR


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