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

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Item Type:	Article
Title:	Functional cross-talk between aldosterone and angiotensin-(1-7) in ventricular myocytes
Creators Name:	Machado de Almeida, P.W., de Freitas Lima, R., de Morais Gomes, E.R., Rocha-Resende, C., Roman-Campos, D., Gondim, A.N.S., Gavioli, M., Lara, A., Parreira, A., de Azevedo Nunes, S.L., Alves, M.N.M., Lauton Santos, S., Alenina, N., Bader, M., Ribeiro Resende, R., dos Santos Cruz, J., 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
Source:	Hypertension
ISSN:	0194-911X
Publisher:	American Heart Association
Volume:	61
Number:	2
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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