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The effects of homocysteine-related compounds on cardiac contractility, coronary flow, and oxidative stress markers in isolated rat heart

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Abstract

Research on the effects of homocysteine on the vascular wall, especially in endothelial and smooth muscle cells, has indicated that increased homocysteine levels lead to cellular stress and cell damage. Considering the adverse effects of homocysteine on vascular function and the role of oxidative stress in these mechanisms, the aim of this study was to estimate the influence of different homocysteine isoforms on cardiac contractility, coronary flow, and oxidative stress markers in isolated rat heart. The hearts of male Wistar albino rats (n = 36, age 8 weeks, body mass 180–200 g), were excised and retrogradely perfused according to the Langendorff technique at a constant perfusion pressure (70 cmH2O) and administered with three isoforms of 10 μM homocysteine [dl-Hcy, dl-Hcy thiolactone-hydrochloride (TLHC) and l-Hcy TLHC). After the insertion and placement of the sensor in the left ventricle, the parameters of heart function: maximum rate of pressure development in the left ventricle (dP/dt max), minimum rate of pressure development in the left ventricle (dP/dt min), systolic left ventricular pressure (SLVP), diastolic left ventricular pressure (DLVP), mean blood pressure (MBP) and heart rate (HR)] were continuously registered. Flowmetry was used to evaluate the coronary flow. Markers of oxidative stress: index of lipid peroxidation measured as TBARS, nitric oxide measured through nitrites (NO2 −), superoxide anion radical (O2 −), and hydrogen peroxide (H2O2) in the coronary venous effluent were assessed spectrophotometrically. Our results showed that administration of Hcy compounds in concentration of 10 μM induced depression of cardiac contractility, manifested by a decrease in dp/dt max after administration of any Hcy compound, decrease in dp/dt min after administration of l-Hcy TLHC, decrease in SLVP after administration of dl-Hcy TLHC and dl-Hcy, and the drop in CF after administration of any Hcy compound. Regarding the effects of Hcy on oxidative stress parameters, only l-Hcy TLHC significantly affected O2 − release. l-Hcy TLHC showed a cardiotoxic effect by affecting heart contractility, but surprisingly, it decreased the release of O2 −.

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Abbreviations

BHMT:

Betaine-homocysteine-methylo-transferase

CAD:

Coronary artery disease

CBS:

Cystathionine β-synthase

CF:

Coronary flow

CPP:

Constant perfusion pressure

CVD:

Cardiovascular disease

eNOS:

Endothelial nitric oxide synthase

Hcy:

Homocysteine

HHcy:

Hyperhomocysteinemia

HRPO:

Peroxidase from horse radish

MDA:

Malondialdehyde

MS:

Methionine synthase

MTHFR:

Methylene-tetrahydrofolate reductase

NBT:

Nitro blue tetrazolium

NO:

Nitric oxide

PRS:

Phenol red solution

TBARS:

Thiobarbituric acid reactive substances

TBA:

Thiobarbituric acid

TLHC:

Thiolactone-hydrochloride

TNF-α:

Tumor necrosis factor alpha

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Acknowledgments

This work is supported by the Grant No. 175043 from the Ministry of Science and Technical Development of the Republic of Serbia and Junior project 04/2011 Faculty of Medicine, University of Kragujevac.

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 Medicine, University of Kragujevac, 69 Svetozara Markovica, 34000, Kragujevac, Serbia

    Vladimir Zivkovic, Vladimir Jakovljevic, Dusica Djordjevic, Milena Vuletic & Nevena Barudzic

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

    Dragan Djuric

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  1. Vladimir Zivkovic
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  2. Vladimir Jakovljevic
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Correspondence to Vladimir Jakovljevic.

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Zivkovic, V., Jakovljevic, V., Djordjevic, D. et al. The effects of homocysteine-related compounds on cardiac contractility, coronary flow, and oxidative stress markers in isolated rat heart. Mol Cell Biochem 370, 59–67 (2012). https://doi.org/10.1007/s11010-012-1398-4

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