title: The effect of intermedin on angiotensin II and endothelin-1 induced ventricular myocyte hypertrophy in neonatal rat.
abstract: BACKGROUND
  Intermedin (IMD), a novel peptide related to calcitonin gene-related peptide (CGRP) and adrenomedullin (ADM), may have localized actions as a modulator of cardiac function. The aim of the study is to explore the effect of IMD on angiotensin II (Ang II) and endothelin-1 (ET-1) induced hypertrophy in ventricular myocytes of neonatal rat and to try to elucidate the possible mechanism.
  
  
  METHODS
  Neonatal rat cardiomyocytes were cultured in serum-free medium with and without AngII (1 micromol/L) or ET-1 (60 micromol/L) in the presence and absence of IMD (1 micromol/L). Hypertrophic responses (including cell surface area, alpha-actin, and beta-myosin heavy chain mRNA expression) and cardiomyocyte expression of NADPH oxidase gp91phox were determined.
  
  
  RESULTS
  Ang II induced increases in cardiomyocyte size to 305 +/- 32 microm2 (n = 198, p < 0.05, at 48 hours), alpha-actin expression to 4 +/- 2.8-fold (n = 6, p < 0.05, at 48 hours) and beta-myosin heavy chain expression to 11 +/- 4.8-fold (n = 6, p < 0.05, at 48 hours), and expression of the gp91phox subunit of NADPH oxidase to 29.4 +/- 12.7-fold (n = 6, p < 0.05, at 48 hours). These effects were all significantly inhibited by IMD; cardiomyocyte size, alpha-actin expression, beta-myosin heavy chain expression, and gp91phox expression were reduced to 265 +/- 32 microm2 (n = 374, p < 0.05), 3.0 +/- 1.7-fold (n = 6, p < 0.05), 8.7 +/- 4.9-fold (n = 6, p < 0.05), 3.9 +/- 3-fold (n = 6, p < 0.05), respectively. IMD also significantly inhibited ET1-induced increases in cardiomyocyte size and superoxide generation.
  
  
  CONCLUSIONS
  IMD exerts an antihypertrophic effect on neonatal cardiomyocytes by reduced levels of superoxide, suggesting that an antioxidant action contributes to the antihypertrophic actions of IMD.
authors.affiliation: Department of Cardiovascular Medicine, West China Hospital, Sichuan University, Chengdu 610041, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Liu
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Deng
authors.forename: Ling
authors.initials: L
authors.lastname: Gong
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Chen
authors.forename: Si
authors.initials: S
authors.lastname: Wang
authors.forename: Hongying
authors.initials: H
authors.lastname: Chen
authors.forename: Xiaoni
authors.initials: X
authors.lastname: Chen
authors.forename: Bogati
authors.initials: B
authors.lastname: Amrit
authors.forename: Sen
authors.initials: S
authors.lastname: He
mesh_terms: D000199:Actins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D053607:Adrenomedullin / Q000494:pharmacology*; D000704:Analysis of Variance; D000804:Angiotensin II / Q000633:toxicity*; D000818:Animals; D000831:Animals, Newborn; D006332:Cardiomegaly / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D048429:Cell Size / Q000187:drug effects; D002478:Cells, Cultured; D004347:Drug Interactions; D019332:Endothelin-1 / Q000633:toxicity*; D015870:Gene Expression / Q000187:drug effects; D006352:Heart Ventricles / Q000166:cytology / Q000187:drug effects; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000166:cytology / Q000187:drug effects* / Q000473:pathology; D018995:Myosin Heavy Chains / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D009479:Neuropeptides / Q000494:pharmacology*; D020011:Protective Agents / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D000199:Actins; C499411:Adm2 protein, rat; D019332:Endothelin-1; C000594638:MYH7 protein, rat; D008562:Membrane Glycoproteins; D009479:Neuropeptides; D020011:Protective Agents; D000804:Angiotensin II; D053607:Adrenomedullin; C500593:Cybb protein, rat; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases; D018995:Myosin Heavy Chains