Increased expression of adrenomedullin 2/intermedin in rat hearts with congestive heart failure.
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.
Hirose
Takuo
T
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
Totsune
Kazuhito
K
Mori
Nobuyoshi
N
Morimoto
Ryo
R
Hashimoto
Masahiro
M
Nakashige
Yukiko
Y
Metoki
Hirohito
H
Asayama
Kei
K
Kikuya
Masahiro
M
Ohkubo
Takayoshi
T
Hashimoto
Junichiro
J
Sasano
Hironobu
H
Kohzuki
Masahiro
M
Takahashi
Kazuhiro
K
Imai
Yutaka
Y
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
D012333:RNA, Messenger; D053607:Adrenomedullin