Increased expression of adrenomedullin 2/intermedin in rat hearts with congestive heart failure |
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Authors: | Hirose Takuo Totsune Kazuhito Mori Nobuyoshi Morimoto Ryo Hashimoto Masahiro Nakashige Yukiko Metoki Hirohito Asayama Kei Kikuya Masahiro Ohkubo Takayoshi Hashimoto Junichiro Sasano Hironobu Kohzuki Masahiro Takahashi Kazuhiro Imai Yutaka |
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Affiliation: | 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. |
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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 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. |
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Keywords: | Adrenomedullin Adrenomedullin 2/Intermedin Heart failure RT‐PCR Immunohistochemistry |
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