1. Functional cross-talk between aldosterone and angiotensin-(1-7) in ventricular myocytes.
- Author
-
de Almeida PW, de Freitas Lima R, de Morais Gomes ER, Rocha-Resende C, Roman-Campos D, Gondim AN, Gavioli M, Lara A, Parreira A, de Azevedo Nunes SL, Alves MN, Santos SL, Alenina N, Bader M, Resende RR, dos Santos Cruz J, Souza dos Santos RA, and Guatimosim S
- Subjects
- Aldosterone pharmacology, Angiotensin I pharmacology, Animals, Calcium Signaling drug effects, Cyclic AMP-Dependent Protein Kinases metabolism, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, Myocytes, Cardiac drug effects, Nitric Oxide metabolism, Peptide Fragments pharmacology, Rats, Rats, Sprague-Dawley, Aldosterone metabolism, Angiotensin I metabolism, Calcium metabolism, Calcium Signaling physiology, Myocytes, Cardiac metabolism, Peptide Fragments metabolism
- 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.
- Published
- 2013
- Full Text
- View/download PDF