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Functional cross-talk between aldosterone and angiotensin-(1-7) in ventricular myocytes

Item Type:Article
Title:Functional cross-talk between aldosterone and angiotensin-(1-7) in ventricular myocytes
Creators Name:Machado de Almeida, P.W. and de Freitas Lima, R. and de Morais Gomes, E.R. and Rocha-Resende, C. and Roman-Campos, D. and Gondim, A.N.S. and Gavioli, M. and Lara, A. and Parreira, A. and de Azevedo Nunes, S.L. and Alves, M.N.M. and Lauton Santos, S. and Alenina, N. and Bader, M. and Ribeiro Resende, R. and dos Santos Cruz, J. and Souza dos Santos, R.A. and Guatimosim, S.
Abstract:High serum levels of aldosterone have been linked to the development of cardiac disease. In contrast, angiotensin (Ang)-(1-7) was extensively shown to possess cardioprotective effects, including the attenuation of cardiac dysfunction induced by excessive mineralocorticoid activation in vivo, suggesting possible interactions between these 2 molecules. Here, we investigated whether there is cross-talk between aldosterone and Ang-(1-7) and its functional consequences for calcium (Ca(2+)) signaling in ventricular myocytes. Short-term effects of aldosterone on Ca(2+) transient were assessed in Fluo-4/AM-loaded myocytes. Confocal images showed that Ang-(1-7) had no effect on Ca(2+) transient parameters, whereas aldosterone increased the magnitude of the Ca(2+) transient. Quite unexpectedly, addition of Ang-(1-7) to aldosterone-treated myocytes further enhanced the amplitude of the Ca(2+) transient suggesting a synergistic effect of these molecules. Aldosterone action on Ca(2+) transient amplitude was mediated by protein kinase A, and was related to an increase in Ca(2+) current (I(Ca)) density. Both changes were not altered by Ang-(1-7). When cardiomyocytes were exposed to aldosterone, increased Ca(2+) spark rate was measured. Ang-(1-7) prevented this change. In addition, a NO synthase inhibitor restored the effect of aldosterone on Ca(2+) spark rate in Ang-(1-7)-treated myocytes and attenuated the synergistic effect of these 2 molecules on Ca(2+) transient. These results indicate that NO plays an important role in this cross-talk. Our results bring new perspectives in the understanding of how 2 prominent molecules with supposedly antagonist cardiac actions cross-talk to synergistically amplify Ca(2+) signals in cardiomyocytes.
Keywords:Calcium, Myocytes, Electrophysiology, Angiotensin, Animals, Mice, Rats
Publisher:American Heart Association
Page Range:425-430
Date:February 2013
Official Publication:https://doi.org/10.1161/HYPERTENSIONAHA.111.199539
PubMed:View item in PubMed

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