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The impact of different diuretics on regression of myocardial reperfusion injury in spontaneously hypertensive rats

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Abstract

The study's objective was to ascertain the results of sub-chronic therapy of various diuretics on the ischemia/reperfusion dysfunction of the heart in hypertensive rats by a global ischemia in an isolated rat heart model. The research included 40 spontaneously hypertensive male rats (Wistar Kyoto strain, body mass 250 ± 30 g, 8 weeks old) grouped into four groups. The animals were treated for 4 weeks with 10 mg/kg of hydrochlorothiazide, indapamide, or spironolactone per os. After a period of sub-chronic treatment, we analyzed hemodynamic measurements, echocardiography, and myocardial function according to the Langendorff retrograde perfusion method. The hearts were subjected to 20 min of global ischemia and then reperfused for 30 min (I20:R30). Cardiovascular parameters that depict the left ventricle functions were continuously monitored, while flowmetry was used to determine coronary flow values. Markers of oxidative stress were estimated from coronary venous effluent using spectrophotometry. All three examined diuretics (hydrochlorothiazide, spironolactone, indapamide) lowered the production of the majority of the detected prooxidants, reducing myocardial oxidative damage. The cardiological examination of heart function in vivo demonstrated that treatment with indapamide and spironolactone mitigates left ventricular hypertrophy but without significant lowering of blood pressure or increment in ejection fraction. Additionally, monitoring of cardiac function ex vivo indicated the cardiodepressant effect of spironolactone in spontaneously hypertensive rats.

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Data are available from the corresponding author upon reasonable request.

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Funding

This research was supported by the Junior Project number 11/22 from the Faculty of Medical Sciences, University of Kragujevac, Serbia.

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Authors and Affiliations

  1. Department of Pharmacy, Faculty of Medical Sciences, University of Kragujevac, Kragujevac, Serbia

    Nevena Dragasevic, Maja Savic, Katarina Mihajlovic, Marijana Andjic, Nevena Draginic & Tamara Nikolic Turnic

  2. Department of Physiology, Faculty of Medical Sciences, University of Kragujevac, Kragujevac, Serbia

    Vladimir Zivkovic & Vladimir Jakovljevic

  3. Department of Pharmacology, 1St Moscow State Medical, University IM Sechenov, Trubetskaya Street 8, Str. 2 119991, Moscow, Russia

    Vladimir Zivkovic

  4. Department of Medical Statistics and Informatics, Faculty of Medical Sciences, University of Kragujevac, Kragujevac, Serbia

    Nebojsa Zdravkovic

  5. Department of Human Pathology, 1St Moscow State Medical, University IM Sechenov, Trubetskaya Street 8, Str. 2 119991, Moscow, Russia

    Nevena Draginic, Sergey Bolevich & Vladimir Jakovljevic

  6. Department of Pathophysiology, 1St Moscow State Medical University IM Sechenov, Moscow, Russia

    Stefani Bolevich

  7. N.A. Semashko Public Health and Healthcare Department, F.F. Erismann Institute of Public Health, I.M. Sechenov First Moscow State Medical University, Moscow, Russia

    Tamara Nikolic Turnic

Authors
  1. Nevena Dragasevic
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  2. Maja Savic
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  3. Katarina Mihajlovic
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  4. Vladimir Zivkovic
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  5. Marijana Andjic
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  6. Nevena Draginic
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  7. Nebojsa Zdravkovic
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  8. Sergey Bolevich
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  9. Stefani Bolevich
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  10. Vladimir Jakovljevic
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Contributions

ND, TNT, and VZ contributed to conceptualization, writing and preparation of the original draft; MA, MS, and KR contributed to validation, visualization, and methodology. SB and SBB contributed to methodology and software. NZ contributed to data curation and visualization. MA, ND, and VLJ contributed to investigation, conceptualization, writing and preparation of the original draft, supervision, and writing, reviewing, and editing of the manuscript.

Corresponding author

Correspondence to Vladimir Jakovljevic.

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Conflict of interest

The authors declare no conflict of interest.

Ethical approval

The study is approved by the Ethics Committee for Laboratory Animal Welfare of the Faculty of Medical Sciences, University of Kragujevac, Serbia.

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Dragasevic, N., Savic, M., Mihajlovic, K. et al. The impact of different diuretics on regression of myocardial reperfusion injury in spontaneously hypertensive rats. Mol Cell Biochem 478, 1803–1812 (2023). https://doi.org/10.1007/s11010-022-04622-x

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  • DOI: https://doi.org/10.1007/s11010-022-04622-x

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