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Angiotensin preconditioning of the heart

Evidence for redox signaling

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Abstract

Angiotensin II (Ang II) has been found to exert preconditioning-like effect on mammalian hearts. Diverse mechanisms are known to exist to explain the cardioprotective abilities of Ang II preconditioning. The present study hypothesized, based on the recent report that Ang II generates reactive oxygen species (ROS) through NADPH oxidase, that Ang II preconditioning occurs through redox cycling. To test this hypothesis, a group of rat hearts was treated with Ang II in the absence or presence of an NADPH oxidase inhibitor, apocynin; or a cell-permeable ROS scavenger, N-acetyl cysteine (NAC). Ang II pretreatment improved postischemic ventricular recovery; reduced myocardial infarction; and decreased the number of cardiomyocyte apoptosis, indicating its ability to precondition the heart against ischemic injury. Both apocynin and NAC almost abolished the preconditioning ability of Ang II. Ang II resulted in increase in ROS activity in the heart, which was reduced by either NAC or apocynin. Ang II also increased both the NADPH oxidase subunits gp91 phox and p22phox mRNA expression, which was abolished with apocynin and NAC. Our results thus demonstrate that the Ang II preconditioning was associated with enhanced ROS activities and increased NADPH oxidase subunits p22phox and gp91phox expression. Both NAC and apocynin reduced ROS activities simultaneously abolishing preconditioning ability of Ang II, suggesting that Ang II preconditioning occurs through redox cycling. That both NAC and apocynin reduced ROS activities and abolished Ang II-mediated increase in p22phox and gp91phox activity further suggest that such redox cycling occurs via both NADPH oxidase-dependent and-independent pathways.

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Authors and Affiliations

  1. Cardiovascular Research Center, University of Connecticut School of Medicine, Farmington, CT

    Samarjit Das, Richard M. Engelman, Nilanjana Maulik & Dipak K. Das

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  1. Samarjit Das
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  2. Richard M. Engelman
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  3. Nilanjana Maulik
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  4. Dipak K. Das
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Correspondence to Dipak K. Das.

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Das, S., Engelman, R.M., Maulik, N. et al. Angiotensin preconditioning of the heart. Cell Biochem Biophys 44, 103–110 (2006). https://doi.org/10.1385/CBB:44:1:103

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