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PMID: 12626668 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Angiotensin II stimulates hyperplasia but not hypertrophy in immature ovine cardiomyocytes.

The Journal of physiology ·Vol. 548 ·No. Pt 3 ·2003-05-01 ·Pages 881-91

Sundgren NC, Giraud GD, Stork PJ, Maylie JG, Thornburg KL

Abstract

Rat and sheep cardiac myocytes become binucleate as they complete the 'terminal differentiation' process soon after birth and are not able to divide thereafter. Angiotensin II (Ang II) is known to stimulate hypertrophic changes in rodent cardiomyocytes under both in vivo and in vitro conditions via the AT1 receptor and intracellular extracellular regulated kinase (ERK) signalling cascade. We sought to develop culture methods for immature sheep cardiomyocytes in order to test the hypothesis that Ang II is a hypertrophic agent in the immature myocardium of the sheep. We isolated fetal sheep cardiomyocytes and cultured them for 96 h, added Ang II and phenylephrine (PE) for 48 h, and measured footprint area and proliferation (5-bromo-2'-deoxyuridine (BrdU) uptake) separately in mono- vs. binucleate myocytes. We found that neither Ang II nor PE changed the footprint area of mononucleated cells. PE stimulated an increase in footprint area of binucleate cells but Ang II did not. Ang II increased myocyte BrdU uptake compared to serum free conditions, but PE did not affect BrdU uptake. The MAP kinase kinase (MEK) inhibitor UO126 prevented BrdU uptake in Ang II-stimulated cells and prevented cell hypertrophy in PE-stimulated cells. This paper establishes culture methods for immature sheep cardiomyocytes and reports that: (1) Ang II is not a hypertrophic agent; (2) Ang II stimulates hyperplastic growth among mononucleate myocytes; (3) PE is a hypertrophic agent in binucleate myocytes; and (4) the ERK cascade is required for the proliferation effect of Ang II and the hypertrophic effect of PE.

MeSH Terms
Angiotensin II/pharmacology Animals Bromodeoxyuridine/pharmacokinetics Cell Culture Techniques/methods Cells, Cultured Female Fetus Gestational Age Heart/drug effects,physiology Heart Ventricles/drug effects,pathology Hyperplasia Hypertrophy Mitogen-Activated Protein Kinases/antagonists & inhibitors Myocardium/pathology Pregnancy Sheep Ventricular Function
Chemicals
Angiotensin II Mitogen-Activated Protein Kinases Bromodeoxyuridine
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Sundgren N C
Department of Physiology, Oregon Health and Science University, Portland, USA.
Giraud G D
Stork P J S
Maylie J G
Thornburg K L
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Article Info
Journal
The Journal of physiology
Abbr.
J Physiol
ISSN
0022-3751
DOI
10.1113/jphysiol.2003.038778
Published
2003-05-01
Epub
2003-00-07
Pages
881-91
Language
English
Region
England
NLM ID
0266262
PMCID
PMC2342902
Subset
IM
Grants
NICHD NIH HHS · P01 HD034430 · United States
NICHD NIH HHS · 2P01 HD34430 · United States
External Links
PubMed source DOI: 10.1113/jphysiol.2003.038778 PMC Full Text View journal details
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