Premium
Atrial natriuretic peptide inhibits angiotensin II‐induced cell proliferation in fetal sheep cardiomyocytes in vitro
Author(s) -
O'Tierney Perrie Faye,
Chattergoon Natasha,
Louey Samantha,
Giraud George,
Thornburg Kent
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.742.2
Subject(s) - atrial natriuretic peptide , medicine , endocrinology , angiotensin ii , bromodeoxyuridine , fetus , cell growth , endothelin 1 , renin–angiotensin system , phenylephrine , muscle hypertrophy , biology , chemistry , receptor , immunohistochemistry , pregnancy , blood pressure , genetics
Objectives: The anti‐hypertrophic properties of atrial natriuretic peptide (ANP) in cardiomyocytes have been well‐demonstrated; ANP inhibits the effects of several potent hypertrophic agents (ie. Angiotensin II, endothelin‐1, phenylephrine). During the last 1/3 of gestation the fetal heart grows by both proliferation and hypertrophy. We hypothesized that ANP also has an anti‐proliferative effect on cardiomyocyte (CMC) growth during fetal development. Methods: Actively dividing cardiomyocytes were isolated from right and left ventricles of late‐gestation fetal sheep. Cultured fetal CMCs were treated with 10uM Bromodeoxyuridine (BrdU) and increasing doses of ANP (3.25, 32.5, 100, 325, 650 nM) with and without 100nM angiotensin II. Following 48 hours of treatment, cells were fixed and stained for myosin and BrdU. BrdU incorporation was used as an index of cell proliferation. Results: Angiotensin II induced BrdU uptake in fetal CMCs and this was inhibited by ANP in a dose‐dependent manner (P=0.024). Physiological doses of ANP alone have no significant effect on BrdU uptake, though at supraphysiological levels (650nM), ANP increased BrdU uptake by fetal CMCs (P=0.051). No significant differences were seen between ventricles. Conclusion: Physiological doses of ANP inhibit fetal cardiomyocyte proliferation induced by angiotensin II. This research was supported by a NICHD (P01HD34430) and a N.L. Tartar Trust research fellowship.