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The effects of cyclooxygenase and nitric oxide synthase inhibition on oxidative stress in isolated rat heart

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An Erratum to this article was published on 28 June 2013

Abstract

Despite the widespread clinical use of cyclooxygenase (COX) inhibitors, dilemmas still exist about potential impact of these drugs on cardiovascular system. The present study was aimed to estimate the effects of different COX inhibitors (meloxicam, acetylsalicylic acid [ASA], and SC-560) on oxidative stress in isolated rat heart, with special focus on l-arginine/NO system. The hearts of male Wistar albino rats (total number n = 96, each group 12 rats, 8 weeks old, body mass 180–200 g) were retrogradely perfused according to the Langendorff technique at gradually increased perfusion pressure (40–120 cmH2O). After control experiments the hearts were perfused with the following drugs: 100 μmol/l ASA (Aspirin), alone or in combination with 30 μmol/l l-NAME, 0.3 μmol/l meloxicam (movalis) with or without 30 μmol/l l-NAME, 3 μmol/l meloxicam (alone or in combination with 30 μmol/l l-NAME), 30 μmol/l l-NAME, and administration of 0.25 μmol/l SC-560. In samples of coronary venous effluent the following oxidative stress markers were measured spectrophotometrically: index of lipid peroxidation (measured as thiobarbituric acid reactive substances [TBARS]), superoxide anion radical release (O2 −), and hydrogen peroxide (H2O2). While ASA was found to have an adverse influence on redox balance in coronary circulation, and coronary perfusion, meloxicam and SC-560 do not negatively affect the intact model of the heart. Furthermore, all effects were modulated by NOS inhibition. It seems that interaction between COX and l-arginine/NO system truly exists in coronary circulation, and can be one of the possible causes for achieved effects. That means: those effects induced by different inhibitors of COX are modulated by subsequent inhibition of NOS.

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Abbreviations

CF:

Coronary flow

CPP:

Coronary perfusion pressure

HRPO:

Peroxidase from horse radish

MDA:

Malonyldialdehyde

COX:

Cyclooxygenase

NOS:

Nitric oxide synthase

MTHFR:

Methylene tetrahydrofolate reductase

NBT:

Nitro blue tetrazolium

NO:

Nitric oxide

PRS:

Phenol red solution

TBARS:

Thiobarbituric acid reactive substances

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Acknowledgments

This work is supported by the Ministry of Science and Technical Development of the Republic of Serbia (Grant No. 175043) and Faculty of Medical Sciences, University of Kragujevac (Junior Project 04/2011). The authors are grateful for technical assistance of Mr. Predrag Ravic and Mr. Andreja Petrovic.

Conflict of interests

All authors of the present paper disclose no actual or potential conflict of interests including any financial, personal, or other relationships with other people or organizations.

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Authors and Affiliations

  1. Department of Physiology, Faculty of Medical Sciences, University of Kragujevac, Svetozara Markovica 69, 34000, Kragujevac, Serbia

    Nevena Barudzic, Vladimir Zivkovic, Dragica Selakovic, Ivan Srejovic, Jovana Jakovljevic & Vladimir Lj. Jakovljevic

  2. Institute of Medical Physiology “Richard Burian”, School of Medicine, University of Belgrade, Belgrade, Serbia

    Drenka Turjacanin-Pantelic & Dragan M. Djuric

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  1. Nevena Barudzic
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  2. Drenka Turjacanin-Pantelic
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Correspondence to Vladimir Lj. Jakovljevic.

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Barudzic, N., Turjacanin-Pantelic, D., Zivkovic, V. et al. The effects of cyclooxygenase and nitric oxide synthase inhibition on oxidative stress in isolated rat heart. Mol Cell Biochem 381, 301–311 (2013). https://doi.org/10.1007/s11010-013-1712-9

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