title: Functional cross-talk between aldosterone and angiotensin-(1-7) in ventricular myocytes.
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.
authors.affiliation: Department of Physiology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Av. Antônio Carlos, 6627 Belo Horizonte, MG-CEP 31270-901, Brazil.
authors.forename: Pedro W Machado
authors.initials: PW
authors.lastname: de Almeida
authors.forename: Ricardo
authors.initials: R
authors.lastname: de Freitas Lima
authors.forename: Enéas Ricardo
authors.initials: ER
authors.lastname: de Morais Gomes
authors.forename: Cibele
authors.initials: C
authors.lastname: Rocha-Resende
authors.forename: Danilo
authors.initials: D
authors.lastname: Roman-Campos
authors.forename: Antonio Nei S
authors.initials: AN
authors.lastname: Gondim
authors.forename: Mariana
authors.initials: M
authors.lastname: Gavioli
authors.forename: Aline
authors.initials: A
authors.lastname: Lara
authors.forename: Amanda
authors.initials: A
authors.lastname: Parreira
authors.forename: Sasha Luísa
authors.initials: SL
authors.lastname: de Azevedo Nunes
authors.forename: Márcia N M
authors.initials: MN
authors.lastname: Alves
authors.forename: Sandra Lauton
authors.initials: SL
authors.lastname: Santos
authors.forename: Natalia
authors.initials: N
authors.lastname: Alenina
authors.forename: Michael
authors.initials: M
authors.lastname: Bader
authors.forename: Rodrigo Ribeiro
authors.initials: RR
authors.lastname: Resende
authors.forename: Jader
authors.initials: J
authors.lastname: dos Santos Cruz
authors.forename: Robson Augusto
authors.initials: RA
authors.lastname: Souza dos Santos
authors.forename: Silvia
authors.initials: S
authors.lastname: Guatimosim
mesh_terms: D000450:Aldosterone / Q000378:metabolism* / Q000494:pharmacology; D000803:Angiotensin I / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism* / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D010446:Peptide Fragments; D009569:Nitric Oxide; D000450:Aldosterone; D000803:Angiotensin I; D017868:Cyclic AMP-Dependent Protein Kinases; C118790:angiotensin I (1-7); D002118:Calcium