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The role of iNOS-derived NO in the antihypertrophic actions of B-type natriuretic peptide in neonatal rat cardiomyocytes

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Abstract

In the infarcted rat heart, the increase of NO occurs in the hypertrophied myocardium of non-infarcted areas and its antihypertrophic efficacy has been well established. As another endogenous regulator and the reliable index of heart pathology, B-type natriuretic peptide also exhibits the antihypertrophic properties in many tissues by elevating intracellular cGMP. Several studies indicate that natriuretic peptides family may exert some actions in part via a nitric oxide pathway following receptor-mediated stimulation of iNOS. Therefore, it raises our great interest to ask what role NO plays in the antihypertrophic actions of B-type natriuretic peptide in cardiomyocytes. Incubation of cardiomyocytes under mild hypoxia for 12 h caused a significant increase in cellular protein content, protein synthesis and cell surface sizes. This growth stimulation was suppressed by exogenous B-type natriuretic peptide in a concentration dependent manner. Furthermore, the generation of intracellular cGMP, the upregulation of iNOS mRNA expression, the increase of iNOS activity and subsequent nitrite generation in hypertrophic cardiomyocytes was also increased by B-type natriuretic peptide. AG, a selective iNOS inhibitor, inhibited the upregulation of iNOS expression and the increase of iNOS activity by the combination of B-type natriuretic peptide/mild hypoxia or by the combination of 8-bromo-cGMP/mild hypoxia. Rp-8-br-cGMP, cGMP dependent protein kinase inhibitor, attenuated the actions of B-type natriuretic peptide and 8-bromo-cGMP which increases intracellular cGMP independent of B-type natriuretic peptide. In conclusion, our present data suggest that B-type natriuretic peptide exerted the antihypertrophic effects in cardiomyocytes, which was partially attributed to induction of iNOS-derived NO by cGMP pathway.

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Acknowledgments

The Research Grant was from the Indonesian Academy of Sciences.

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Authors and Affiliations

  1. Department of Biomedical Engineering, Zhejiang University (Yuquan Campus), Hangzhou, 310027, P.R. China

    Tiannan Wang, Ming Yan, Jieyue Li & Xiaoxiang Zheng

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  1. Tiannan Wang
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  2. Ming Yan
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Correspondence to Xiaoxiang Zheng.

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Wang, T., Yan, M., Li, J. et al. The role of iNOS-derived NO in the antihypertrophic actions of B-type natriuretic peptide in neonatal rat cardiomyocytes. Mol Cell Biochem 302, 169–177 (2007). https://doi.org/10.1007/s11010-007-9438-1

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  • DOI: https://doi.org/10.1007/s11010-007-9438-1

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