Effect of intermedin1-53 on angiotensin II-induced hypertrophy in neonatal rat ventricular myocytes.
OBJECTIVE
Intermedin (IMD) is coexpressed in the heart with its receptor, which suggests that it may have localized actions as a modulator of cardiac function. The present study was designed to observe the interaction between IMD and cardiac hypertrophy and the possible mechanism involved in the antihypertrophic effects of IMD1-53 in cultured neonatal ventricular myocytes.


METHODS
Myocyte hypertrophy was induced by treating the cells with angiotensin II, and the hypertrophic response was characterized by a significant increase in cell surface area, protein synthesis, and BNP mRNA expression.


RESULTS
Our results showed that angiotensin II led to an obvious decrease in the production, secretion, and mRNA expression of IMD and increase receptor activity modifying proteins 1, 3 mRNA expression. Moreover, IMD1-53 inhibited the angiotensin II-induced hypertrophic response and the effects of IMD1-53 were similar to those of equivalent-dose adrenomedullin and could been blocked by H89. Otherwise, in our study, IMD1-53 resulted in dose-dependent increases of cAMP production in cardiomyocytes.


CONCLUSIONS
Thus, IMD and its receptor system are involved in cardiac hypertrophy, and like adrenomedullin, IMD1-53 exerts an antihypertrophic effect on neonatal cardiomyocytes and the effect can be mediated by the cAMP/PKA pathway.
Yang
Jing-Hui
JH
Institute of Brain Science, Shanxi Datong University School of Medical Science, Datong, Shanxi, PR China.
Ma
Cun-Gen
CG
Cai
Yan
Y
Pan
Chun-Shui
CS
Zhao
Jing
J
Tang
Chao-Shu
CS
Qi
Yong-Fen
YF
D053607:Adrenomedullin / Q000008:administration & dosage / Q000378:metabolism* / Q000494:pharmacology; D000804:Angiotensin II / Q000633:toxicity; D000818:Animals; D000831:Animals, Newborn; D006332:Cardiomegaly / Q000503:physiopathology*; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D006352:Heart Ventricles / Q000166:cytology / Q000503:physiopathology; D032383:Myocytes, Cardiac / Q000378:metabolism* / Q000473:pathology; D020097:Natriuretic Peptide, Brain / Q000235:genetics; D009479:Neuropeptides / Q000008:administration & dosage / Q000378:metabolism* / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
C499411:Adm2 protein, rat; D009479:Neuropeptides; D012333:RNA, Messenger; D000804:Angiotensin II; D020097:Natriuretic Peptide, Brain; D053607:Adrenomedullin; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases