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Oxygen/ozone protects the heart from acute myocardial infarction through local increase of eNOS activity and endothelial progenitor cells recruitment

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Abstract

The purpose of this study is to investigate whether an oxygen/ozone (O2/O3) mixture protects the heart from acute myocardial infarction through local involvement of endothelial nitric oxide synthase (eNOS) and endothelial progenitor cells (EPCs). Male Sprague–Dawley rats were subject to 25-min occlusion and 2-h reperfusion of the left descending coronary artery. O2/O3 mixture was insufflated i.p. 30 min prior to ischemia/reperfusion (I/R) procedure at doses of 100, 150, and 300 μg/kg. Myocardial infarct size (IS) measurement and myocardial immunohistochemistry for EPCs were done. For these latter cells, immunoreactivities for CD34, and CD117/c-kit were assessed within the infarcted tissue. Moreover, cardiac eNOS was monitored. I/R in rats treated with O2 produced an IS as a percentage of the area at risk (IS/AR) equal to 51 ± 5%. I/R in rats treated with the O2/O3 mixture showed reduced IS (for example, IS/AR for 150 μg/kg O2/O3 was 35 ± 2.1%; P < 0.01 vs. O2). The O2/O3 cardio-protection was paralleled by an increased number of immunopositive particles per area for CD34 and CD117/c-kit. The increase of these markers was associated with an increase of cardiac eNOS expression as assayed by immunohistochemistry. Interestingly, N5-(1-Iminoethyl)-L-ornithine dihydrochloride (L-NIO), a selective eNOS activity inhibitor (30 mg/kg s.c.), prior to O2/O3 and I/R almost abolished the cardio-protection exerted by the O2/O3 mixture. L-NIO also abolished the increase in immunostaining for CD-34 and CD117/c-kit as compared with the rats receiving O2/O3 and I/R only. O2/O3 mixture protects the heart from acute myocardial infarction through local increase of eNOS expression/activity and consequent EPCs recruitment.

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Acknowledgements

The authors acknowledge the surgical help of Prof Pasquale Petronella from the Second University of Naples.

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Experimental Medicine, Section of Pharmacology “L. Donatelli”, Second University of Naples, Via Costantinopoli 16, 80138, Naples, Italy

    Clara Di Filippo, Annalisa Capuano, Francesco Rossi & Michele D’Amico

  2. Department of Anaestesiological, Surgical and Emergency Sciences, Second University of Naples, Naples, Italy

    Margherita Luongo & Biagio Lettieri

  3. Department of Geriatrics and Metabolic Diseases, Second University of Naples, Naples, Italy

    Raffaele Marfella

  4. Department of Clinical, Public and Preventive Medicine, Second University of Naples, Naples, Italy

    Franca Ferraraccio

Authors
  1. Clara Di Filippo
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  2. Margherita Luongo
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  3. Raffaele Marfella
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  4. Franca Ferraraccio
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  5. Biagio Lettieri
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  6. Annalisa Capuano
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  7. Francesco Rossi
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  8. Michele D’Amico
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Corresponding author

Correspondence to Clara Di Filippo.

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Di Filippo, C., Luongo, M., Marfella, R. et al. Oxygen/ozone protects the heart from acute myocardial infarction through local increase of eNOS activity and endothelial progenitor cells recruitment. Naunyn-Schmied Arch Pharmacol 382, 287–291 (2010). https://doi.org/10.1007/s00210-010-0545-2

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  • DOI: https://doi.org/10.1007/s00210-010-0545-2

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