Antioxidant actions contribute to the antihypertrophic effects of atrial natriuretic peptide in neonatal rat cardiomyocytes

Laskowski, A, Woodman, O, Cao, A, Dummond, G, Marshall, T, Kaye, D and Ritchie, R 2006, 'Antioxidant actions contribute to the antihypertrophic effects of atrial natriuretic peptide in neonatal rat cardiomyocytes', Cardiovascular Research, vol. 72, no. 1, pp. 112-123.


Document type: Journal Article
Collection: Journal Articles

Title Antioxidant actions contribute to the antihypertrophic effects of atrial natriuretic peptide in neonatal rat cardiomyocytes
Author(s) Laskowski, A
Woodman, O
Cao, A
Dummond, G
Marshall, T
Kaye, D
Ritchie, R
Year 2006
Journal name Cardiovascular Research
Volume number 72
Issue number 1
Start page 112
End page 123
Total pages 12
Publisher Elsevier
Abstract Objective: Reactive oxygen species (ROS) such as superoxide have been linked to the hypertrophic response of the heart to stimuli including angiotensin II (AngII), mechanical stretch, and pressure overload. We have previously demonstrated that cGMP and protein kinase G mediate the antihypertrophic actions of the natriuretic peptides in rat cardiomyocytes and isolated whole hearts. The impact of natriuretic peptides on cardiac ROS generation, however, has not been investigated. We tested the hypothesis that reduced superoxide accumulation contributes to the antihypertrophic action of atrial natriuretic peptide (ANP). Methods: Neonatal rat cardiomyocytes were cultured in serum-free medium with and without AngII (1 ?mol/L) or endothelin-1 (ET1, 60 nmol/L) in the presence and absence of ANP (1 ?mol/L) or tempol (100 ?mol/L). Hypertrophic responses, cardiomyocyte superoxide generation, and cardiomyocyte expression of NADPH oxidase were determined. Results: AngII induced increases in cardiomyocyte size (to 176 ± 9% n = 8 p < 0.001, at 48 h), ?-myosin heavy chain expression (to 4.0 ± 1.6-fold n = 6 p < 0.05, at 48 h), c-fos expression (to 1.9 ± 0.5-fold n = 7 p < 0.01, at 6 h), superoxide generation (to 181 ± 21% n = 8 p < 0.005, at 24 h), and expression of the gp91phox subunit of NADPH oxidase (to 2.4 ± 0.5-fold n = 7 p < 0.05, at 48 h). These effects were all significantly inhibited by ANP: cardiomyocyte size, ?-myosin heavy chain expression, c-fos expression, superoxide generation and gp91phox expression were reduced to 107 ± 5% (n = 5 p < 0.05), 1.2 ± 0.2-fold (n = 6 p < 0.05), 0.9 ± 0.2-fold (n = 7 p < 0.05), 141 ± 21% (n = 8 p < 0.05), and to 1.0 ± 0.5-fold (n = 7 p < 0.05), respectively. These effects were mimicked by tempol. ANP and tempol also significantly inhibited ET1-induced increases in cardiomyocyte size and superoxide generation, but had no effect on markers of hypertrophy when studied alone.
Subject Basic Pharmacology
Cardiovascular Medicine and Haematology not elsewhere classified
Clinical Sciences not elsewhere classified
Keyword(s) ANP
Antioxidant
Cardiomyocytes
NADPH oxidase
Oxygen radicals
Peptide hormones
DOI - identifier 10.1016/j.cardiores.2006.07.006
Copyright notice © 2006 European Society of Cardiology. Published by Elsevier B.V. All rights reserved.
ISSN 0008-6363
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