Atrial natriuretic peptide induces apoptosis in neonatal rat cardiac myocytes

Can Fang Wu, Nanette Bishopric, Richard E. Pratt

Research output: Contribution to journalArticle

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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 μM 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 β-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.

Original languageEnglish
Pages (from-to)14860-14866
Number of pages7
JournalJournal of Biological Chemistry
Volume272
Issue number23
DOIs
StatePublished - Jun 6 1997

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Atrial Natriuretic Factor
Cardiac Myocytes
Rats
Apoptosis
Norepinephrine
Phosphodiesterase Inhibitors
Guanylate Cyclase
Cyclic GMP
Nitroprusside
Cyclic AMP
Adrenergic Receptors
Muscle Cells
Intercellular Signaling Peptides and Proteins
Heart Failure
Chemical activation
Cells
Modulation
Membranes
Plasmas
Messenger RNA

ASJC Scopus subject areas

  • Biochemistry

Cite this

Atrial natriuretic peptide induces apoptosis in neonatal rat cardiac myocytes. / Wu, Can Fang; Bishopric, Nanette; Pratt, Richard E.

In: Journal of Biological Chemistry, Vol. 272, No. 23, 06.06.1997, p. 14860-14866.

Research output: Contribution to journalArticle

Wu, Can Fang ; Bishopric, Nanette ; Pratt, Richard E. / Atrial natriuretic peptide induces apoptosis in neonatal rat cardiac myocytes. In: Journal of Biological Chemistry. 1997 ; Vol. 272, No. 23. pp. 14860-14866.
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