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Updated: Sep 17, 2026
Isolation and Cryopreservation of Neonatal Rat Cardiomyocytes
Published on: April 9, 2015
Atrial natriuretic peptide induces apoptosis in neonatal rat cardiac myocytes
C F Wu1, N H Bishopric, R E Pratt
1Falk Cardiovascular Research Center, Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, California 94305, USA.
Abstract:
Early heart failure is characterized by elevated plasma atrial natriuretic peptide (ANP) levels, but little is known about the direct effects of ANP on cardiac myocytes. In neonatal rat cardiac myocytes, ANP induced apoptosis in a dose-dependent and cell type-specific manner. Maximum effects occurred at 1 microM ANP, with a 4-5-fold increase in apoptotic cells, reaching a maximum apoptotic index of 19%. In contrast, the maximum apoptotic index of ANP-treated non-myocytes was 1.1 +/- 0.2%, equivalent to control cultures. ANP treatment also sharply reduced levels of Mcl-1 mRNA, a Bcl-2 homologue, coincident with the increase in the incidence of apoptosis. ANP induction of apoptosis was receptor-dependent and mediated by cyclic GMP: the effect was mimicked by 8-bromo-cGMP, a membrane-permeable analog, and by sodium nitroprusside, an activator of soluble guanylyl cyclase, and was potentiated by a cGMP-specific phosphodiesterase inhibitor, zaprinast. Interestingly, norepinephrine, a myocyte growth factor, inhibited ANP-induced apoptosis via activation of the beta-adrenergic receptor and elevation of cyclic AMP. These results show that ANP is a specific effector of cardiac myocyte apoptosis in culture via receptor-mediated elevation of cGMP. Furthermore, at least in this model, ANP and norepinephrine may have opposing roles in the modulation of cardiac myocyte growth and survival.
Insights
Atrial natriuretic peptide (ANP) directly triggers cardiac myocyte apoptosis in neonatal rats by increasing cyclic GMP. Norepinephrine counteracts this effect, suggesting opposing roles in heart cell survival.
Area of Science:
- Cardiology
- Molecular Biology
- Cell Biology
Background:
- Elevated plasma atrial natriuretic peptide (ANP) levels are observed in early heart failure.
- The direct impact of ANP on cardiac myocytes remains largely uncharacterized.
Purpose of the Study:
- To investigate the direct effects of ANP on neonatal rat cardiac myocytes.
- To elucidate the signaling pathways involved in ANP-mediated cardiac myocyte apoptosis.
Main Methods:
- Primary cultures of neonatal rat cardiac myocytes and non-myocytes were treated with varying concentrations of ANP.
- Messenger RNA (mRNA) levels of Mcl-1, a Bcl-2 homologue, were assessed.
- Apoptosis was induced and measured using specific analogs and inhibitors of cyclic GMP (cGMP) and cyclic AMP (cAMP) pathways.
- The role of beta-adrenergic receptor activation by norepinephrine was also examined.
Main Results:
- ANP induced apoptosis in cardiac myocytes in a dose-dependent manner, increasing the apoptotic index up to 19%.
- ANP treatment significantly reduced Mcl-1 mRNA levels, correlating with increased apoptosis.
- ANP-induced apoptosis was confirmed to be receptor-dependent and mediated by cGMP.
- Norepinephrine inhibited ANP-induced apoptosis by activating the beta-adrenergic receptor and elevating cAMP.
Conclusions:
- ANP acts as a specific inducer of cardiac myocyte apoptosis in vitro through receptor-mediated cGMP elevation.
- ANP and norepinephrine may play opposing roles in regulating cardiac myocyte growth and survival in this model.
