Mitochondrial reactive oxygen species activate the slow force response to stretch in feline myocardium

Caldiz, Claudia Irma; Garciarena, Carolina D.; Dulce, Raúl A; Novaretto, Leonardo P.; Yeves, Alejandra del Milagro; Ennis, Irene L.; Cingolani, Horacio E.; Cingolani, Gladys E. Chiappe de; Pérez, Néstor Gustavo

doi:10.1113/jphysiol.2007.141689

Cited by 79 publications

(138 citation statements)

References 43 publications

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“…1 Myocardial stretch induces NHE1 phosphorylation at Ser703 13 through a mechanism that involves redox-induced activation of ERK1/2 and p90 RSK . 13,14 As expected, we detected a significant increase in ERK1/2 and p90 RSK phosphorylation after stretching control-injected papillary muscles, an effect that was considerably blunted in muscles from MR-silenced hearts ( Figure 5). Therefore, an activated MR is a necessary condition to induce redox-sensitive kinase activation after myocardial stretch.…”

Section: Resultssupporting

confidence: 51%

Myocardial Mineralocorticoid Receptor Activation by Stretching and Its Functional Consequences

et al. 2014

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Abstract-Myocardial stretch triggers an angiotensin II-dependent autocrine/paracrine loop of intracellular signals, leading to reactive oxygen species-mediated activation of redox-sensitive kinases. Based on pharmacological strategies, we previously proposed that mineralocorticoid receptor (MR) is necessary for this stretch-triggered mechanism. Now, we aimed to test the role of MR after stretch by using a molecular approach to avoid secondary effects of pharmacological MR blockers. Small hairpin interference RNA capable of specifically knocking down the MR was incorporated into a lentiviral vector (l-shMR) and injected into the left ventricular wall of Wistar rats. The same vector but expressing a nonsilencing sequence (scramble) was used as control. Lentivirus propagation through the left ventricle was evidenced by confocal microscopy. Myocardial MR expression, stretch-triggered activation of redoxsensitive kinases (ERK1/2-p90 RSK ), the consequent Na + /H + exchanger-mediated changes in pH i (HEPES-buffer), and its mechanical counterpart, the slow force response, were evaluated. Furthermore, reactive oxygen species production in response to a low concentration of angiotensin II (1.0 nmol/L) or an equipotent concentration of epidermal growth factor (0.1 μg/mL) was compared in myocardial tissue slices from both groups. Compared with scramble, animals transduced with l-shMR showed (1) reduced cardiac MR expression, (2) cancellation of angiotensin II-induced reactive oxygen species production but preservation of epidermal growth factor-induced reactive oxygen species production, (3) cancellation of stretch-triggered increase in ERK1/2-p90 RSK phosphorylation, (4)

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Section: Resultssupporting

confidence: 51%

Myocardial Mineralocorticoid Receptor Activation by Stretching and Its Functional Consequences

et al. 2014

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“…It is not known whether trout myocardium possess NHE, but our preliminary work (D. E. Warren and H.A.S., unpublished observations) suggests that, if present, it is not robust. Interestingly, a recent study has suggested a pivotal role for mitochondrial reactive oxygen species in the generation of the SFR by activation of NHE (Caldiz et al, 2007). If this is the case, the high antioxidant activity found within the trout heart, as opposed to a lack of NHE, may explain the lack of the SFR in trout ventricular tissue (Trenzado et al, 2006).…”

Section: Discussionmentioning

confidence: 99%

“…A second, slower, stretch-induced increase in contractility was identified in cat papillary muscle (Parmley and Chuck, 1973) and has since been observed in preparations ranging from single cardiac cells to whole hearts in a number of mammalian species (Allen and Kurihara, 1982;Alvarez et al, 1999;von Lewinski et al, 2004;Calaghan and White, 2004;Caldiz et al, 2007). This slow positive inotropic response occurs over the minutes following the initial stretch and is known as the slow force response (SFR).…”

Section: Introductionmentioning

confidence: 99%

Rainbow trout myocardium does not exhibit a slow inotropic response to stretch

Patrick

White

Shiels

2011

Journal of Experimental Biology

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SUMMARYMammalian myocardial studies reveal a biphasic increase in the force of contraction due to stretch. The first rapid response, known as the Frank-Starling response, occurs within one heartbeat of stretch. A second positive inotropic response occurs over the minutes following the initial stretch and is known as the slow force response (SFR). The SFR has been observed in mammalian isolated whole hearts, muscle preparations and individual myocytes. We present the first direct study into the SFR in the heart of a non-mammalian vertebrate, the rainbow trout (Oncorhynchus mykiss). We stretched ventricular trabecular muscle preparations from 88% to 98% of their optimal length and individual ventricular myocytes by 7% of their slack sarcomere length (SL). Stretch caused an immediate increase in force in both preparations, indicative of the Frank-Starling response. However, we found no significant effect of prolonged stretch on the force of contraction in either the ventricular trabecular preparations or the single myocytes. This indicates that rainbow trout ventricular myocardium does not exhibit a SFR and that, in contrast to mammals, the piscine Frank-Starling response may not be associated with the SFR. We speculate that this is due to the fish myocardium modulating cardiac output via changes in stroke volume to a larger extent than heart rate.

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“…29 An expanded Methods section is available in the online Data Supplement at http://hypertension.ahajournals.org.…”

Section: Measurements Of Superoxide Anion Productionmentioning

confidence: 99%

Aldosterone Stimulates the Cardiac Na ⁺ /H ⁺ Exchanger via Transactivation of the Epidermal Growth Factor Receptor

et al. 2011

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Abstract-The use of antagonists of the mineralocorticoid receptor in the treatment of myocardial hypertrophy and heart failure has gained increasing importance in the last years. The cardiac Na ϩ /H ϩ exchanger (NHE-1) upregulation induced by aldosterone could account for the genesis of these pathologies. We tested whether aldosterone-induced NHE-1 stimulation involves the transactivation of the epidermal growth factor receptor (EGFR). Rat ventricular myocytes were used to measure intracellular pH with epifluorescence. Aldosterone enhanced the NHE-1 activity. This effect was canceled by spironolactone or eplerenone (mineralocorticoid receptor antagonists), but not by mifepristone (glucocorticoid receptor antagonist) or cycloheximide (protein synthesis inhibitor), indicating that the mechanism is mediated by the mineralocorticoid receptor triggering nongenomic pathways. Aldosterone-induced NHE-1 stimulation was abolished by the EGFR kinase inhibitor AG1478, suggesting that is mediated by transactivation of EGFR. The increase in the phosphorylation level of the kinase p90 RSK and NHE-1 serine703 induced by aldosterone was also blocked by AG1478. Exogenous epidermal growth factor mimicked the effects of aldosterone on NHE-1 activity. Epidermal growth factor was also able to increase reactive oxygen species production, and the epidermal growth factor-induced activation of the NHE-1 was abrogated by the reactive oxygen species scavenger N-2-mercaptopropionyl glycine, indicating that reactive oxygen species are participating as signaling molecules in this mechanism. Aldosterone enhances the NHE-1 activity via transactivation of the EGFR, formation of reactive oxygen species, and phosphorylation of the exchanger. These results call attention to the consideration of the EGFR as a new potential therapeutic target of the cardiovascular pathologies involving the participation of aldosterone. [1][2][3][4] Aldosterone has been shown to induce left ventricular hypertrophy independently from its classic effects on regulation of renal Na ϩ and blood pressure. 5-7 However, the cellular, subcellular, and molecular bases for this effect are not yet understood. Fujisawa et al 8 demonstrated that the mineralocorticoid/salt-induced rat cardiac fibrosis and hypertrophy were prevented by the selective Na ϩ /H ϩ exchanger (NHE-1) blocker cariporide. It has also been reported that aldosterone upregulates the expression and function of the NHE-1 9 -12 and that selective blockade of this transporter prevents and/or reverts left ventricular hypertrophy in various animal models. 13 Therefore, we focused our attention on the intracellular pathway that involves aldosterone and NHE-1 as trigger and end point target, respectively.Steroids, including aldosterone, are able to interact with peptide hormone signaling. The epidermal growth factor (EGF) and its receptor (EGFR) represent one of these signals involving aldosterone. 14,15 It has been shown that spironolactone reduces the EGFR mRNA synthesis after cerebral ischemia. 16 Accordingly, Gross...

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Mitochondrial reactive oxygen species activate the slow force response to stretch in feline myocardium

Cited by 79 publications

References 43 publications

Myocardial Mineralocorticoid Receptor Activation by Stretching and Its Functional Consequences

Myocardial Mineralocorticoid Receptor Activation by Stretching and Its Functional Consequences

Rainbow trout myocardium does not exhibit a slow inotropic response to stretch

Aldosterone Stimulates the Cardiac Na ⁺ /H ⁺ Exchanger via Transactivation of the Epidermal Growth Factor Receptor

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Mitochondrial reactive oxygen species activate the slow force response to stretch in feline myocardium

Cited by 79 publications

References 43 publications

Myocardial Mineralocorticoid Receptor Activation by Stretching and Its Functional Consequences

Myocardial Mineralocorticoid Receptor Activation by Stretching and Its Functional Consequences

Rainbow trout myocardium does not exhibit a slow inotropic response to stretch

Aldosterone Stimulates the Cardiac Na + /H + Exchanger via Transactivation of the Epidermal Growth Factor Receptor

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Aldosterone Stimulates the Cardiac Na ⁺ /H ⁺ Exchanger via Transactivation of the Epidermal Growth Factor Receptor