Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Success of Nitric Oxide System Modulators in Pharmacocorrection of Some Indicators of Endothelial Dysfunction After Intrauterine Hypoxia

Igor Belenichev
ORCID logo ,
Olena Popazova
* ORCID logo ,
Oleh Yadlovskyi
,
Nina Bukhtiyarova
,
Victor Ryzhenko
,
Sergii V. Pavlov
ORCID logo ,
Valentyn Oksenych
* ORCID logo ,
Oleksandr Kamyshnyi
Version 1 : Received: 31 October 2024 / Approved: 3 November 2024 / Online: 4 November 2024 (10:49:10 CET)

How to cite: Belenichev, I.; Popazova, O.; Yadlovskyi, O.; Bukhtiyarova, N.; Ryzhenko, V.; Pavlov, S. V.; Oksenych, V.; Kamyshnyi, O. Success of Nitric Oxide System Modulators in Pharmacocorrection of Some Indicators of Endothelial Dysfunction After Intrauterine Hypoxia. Preprints 2024, 2024110122. https://doi.org/10.20944/preprints202411.0122.v1 Belenichev, I.; Popazova, O.; Yadlovskyi, O.; Bukhtiyarova, N.; Ryzhenko, V.; Pavlov, S. V.; Oksenych, V.; Kamyshnyi, O. Success of Nitric Oxide System Modulators in Pharmacocorrection of Some Indicators of Endothelial Dysfunction After Intrauterine Hypoxia. Preprints 2024, 2024110122. https://doi.org/10.20944/preprints202411.0122.v1

Abstract

Prenatal hypoxia plays a crucial role in programming long-term cardiovascular dysfunction through mechanisms like endothelial dysfunction and nitric oxide system impairment, highlighting the potential of therapeutic agents, such as thiotriazoline, angiolin, mildronate, and L-arginine, for mitigating these adverse effects. Methods. Levels of sEPCR, Tie2 tyrosine kinase, VEGF-B, SOD1/Cu-Zn SOD, GPX4, and GPX1 were measured in the heart's cytosolic homogenate using ELISA. Results. Modeling prenatal hypoxia (PH) resulted in significant alterations in the concentrations of proteins linked to endothelial function and oxidative stress in the heart cytosol of experimental animals, including an increase in sEPCR and reductions in Tie-2, VEGF-B, Cu/ZnSOD, GPX4, and GPX1 levels. Postnatal administration of nitric oxide modulators (L-arginine, thiotriazoline, angiolin, and mildronate) demonstrated differential efficacy in normalizing these proteins. Notably, angiolin produced the most substantial therapeutic effect, restoring Tie2, VEGF-B, and antioxidant enzyme levels to near-normal levels. Our results highlight the efficacy of Angiolin and Thiotriazoline in restoring endothelial function and antioxidant enzyme levels in the car-diovascular system following prenatal hypoxia, supporting their potential as early postnatal in-terventions to prevent long-term cardiovascular dysfunction.

Keywords

prenatal hypoxia; cardioprotective; Angiolin; L-arginine; Thiotriazoline; Mildronate; сEPCR; Tie-2; VEGF-B; Cu/ZnSOD; GPX1; GPX4

Subject

Medicine and Pharmacology, Cardiac and Cardiovascular Systems

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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