title: Increased expression of adrenomedullin 2/intermedin in rat hearts with congestive heart failure.
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.
authors.affiliation: Department of Clinical Pharmacology and Therapeutics, Tohoku University Graduate School of Pharmaceutical Sciences and Medicine, 6-3 Aramaki-aza-aoba, Sendai 980-8578, Japan. hirose-t@m.tains.tohoku.ac.jp
authors.forename: Takuo
authors.initials: T
authors.lastname: Hirose
authors.forename: Kazuhito
authors.initials: K
authors.lastname: Totsune
authors.forename: Nobuyoshi
authors.initials: N
authors.lastname: Mori
authors.forename: Ryo
authors.initials: R
authors.lastname: Morimoto
authors.forename: Masahiro
authors.initials: M
authors.lastname: Hashimoto
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Nakashige
authors.forename: Hirohito
authors.initials: H
authors.lastname: Metoki
authors.forename: Kei
authors.initials: K
authors.lastname: Asayama
authors.forename: Masahiro
authors.initials: M
authors.lastname: Kikuya
authors.forename: Takayoshi
authors.initials: T
authors.lastname: Ohkubo
authors.forename: Junichiro
authors.initials: J
authors.lastname: Hashimoto
authors.forename: Hironobu
authors.initials: H
authors.lastname: Sasano
authors.forename: Masahiro
authors.initials: M
authors.lastname: Kohzuki
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Takahashi
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Imai
mesh_terms: D053607:Adrenomedullin / Q000235:genetics* / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D015870:Gene Expression; D006333:Heart Failure / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D007124:Immunoenzyme Techniques; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D012333:RNA, Messenger; D053607:Adrenomedullin