Possibility of Using NO Modulators for Pharmacocorrection of Endothelial Dysfunction After Prenatal Hypoxia
Prenatal hypoxia (PH) is a key factor in the development of long-term cardiovascular disorders, which are caused by various mechanisms of endothelial dysfunction (ED), including those associated with NO deficiency. This emphasizes the potential of therapeutic agents with NO modulator properties, suc...
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2025-01-01
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| author | Igor Belenichev Olena Popazova Oleh Yadlovskyi Nina Bukhtiyarova Victor Ryzhenko Sergii Pavlov Valentyn Oksenych Oleksandr Kamyshnyi |
| author_facet | Igor Belenichev Olena Popazova Oleh Yadlovskyi Nina Bukhtiyarova Victor Ryzhenko Sergii Pavlov Valentyn Oksenych Oleksandr Kamyshnyi |
| author_sort | Igor Belenichev |
| collection | DOAJ |
| description | Prenatal hypoxia (PH) is a key factor in the development of long-term cardiovascular disorders, which are caused by various mechanisms of endothelial dysfunction (ED), including those associated with NO deficiency. This emphasizes the potential of therapeutic agents with NO modulator properties, such as Thiotriazoline, Angiolin, Mildronate, and L-arginine, in the treatment of PH. <b>Methods:</b> Pregnant female rats were given a daily intraperitoneal dose of 50 mg/kg of sodium nitrite starting on the 16th day of pregnancy. A control group of pregnant rats received saline instead. The resulting offspring were divided into the following groups: Group 1—intact rats; Group 2—rat pups subjected to prenatal hypoxia (PH) and treated daily with physiological saline; and Groups 3 to 6—rat pups exposed to prenatal hypoxia and treated daily from the 1st to the 30th day after birth. Levels of sEPCR, Tie2 tyrosine kinase, VEGF-B, SOD1/Cu-Zn SOD, GPX4, and GPX1 in the heart’s cytosolic homogenate were assessed using ELISA. The expression of VEGF and VEGF-B mRNA was analyzed via real-time polymerase chain reaction, and the nuclear area of myocardial microvessel endothelial cells was evaluated morphometrically. <b>Results:</b> We have shown that only two representatives of this group—Angiolin and Thiotriazoline—are able to exert full effect on the indices of endothelial dysfunction after PH to decrease sEPCR, increase Tie-2, VEGF-B and VEGF-B mRNA, Cu/ZnSOD, and GPX in myocardial cytosol, and increase the area of endotheliocyte nuclei in 1- and 2-month-old rats in comparison with the control. <b>Conclusions:</b> Our results experimentally substantiate the necessity of early postnatal cardio- and endothelioprotection using NO modulators, taking into account the role of NO-dependent mechanisms in the pathogenesis of cardiovascular system disorders in neonates after PH. |
| format | Article |
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| institution | Kabale University |
| issn | 1424-8247 |
| language | English |
| publishDate | 2025-01-01 |
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| series | Pharmaceuticals |
| spelling | doaj-art-a4b03317b5da4baa91d5a8f9564fcbea2025-01-24T13:45:25ZengMDPI AGPharmaceuticals1424-82472025-01-0118110610.3390/ph18010106Possibility of Using NO Modulators for Pharmacocorrection of Endothelial Dysfunction After Prenatal HypoxiaIgor Belenichev0Olena Popazova1Oleh Yadlovskyi2Nina Bukhtiyarova3Victor Ryzhenko4Sergii Pavlov5Valentyn Oksenych6Oleksandr Kamyshnyi7Department of Pharmacology and Medical Formulation with Course of Normal Physiology, Zaporizhzhia State Medical and Pharmaceutical University, 69000 Zaporizhzhia, UkraineDepartment of Histology, Cytology and Embryology, Zaporizhzhia State Medical and Pharmaceutical University, 69000 Zaporizhzhia, UkraineInstitute of Pharmacology and Toxicology, National Medical Academy of Ukraine, 03057 Kyiv, UkraineDepartment of Clinical Laboratory Diagnostics, Zaporizhzhia State Medical and Pharmaceutical University, 69000 Zaporizhzhia, UkraineDepartment of Medical and Pharmaceutical Informatics and Advanced Technologies, Zaporizhzhia State Medical University, 69000 Zaporizhzhia, UkraineDepartment of Clinical Laboratory Diagnostics, Zaporizhzhia State Medical and Pharmaceutical University, 69000 Zaporizhzhia, UkraineFaculty of Medicine, University of Bergen, 5020 Bergen, NorwayDepartment of Microbiology, Virology and Immunology, I. Horbachevsky Ternopil State Medical University, 46001 Ternopil, UkrainePrenatal hypoxia (PH) is a key factor in the development of long-term cardiovascular disorders, which are caused by various mechanisms of endothelial dysfunction (ED), including those associated with NO deficiency. This emphasizes the potential of therapeutic agents with NO modulator properties, such as Thiotriazoline, Angiolin, Mildronate, and L-arginine, in the treatment of PH. <b>Methods:</b> Pregnant female rats were given a daily intraperitoneal dose of 50 mg/kg of sodium nitrite starting on the 16th day of pregnancy. A control group of pregnant rats received saline instead. The resulting offspring were divided into the following groups: Group 1—intact rats; Group 2—rat pups subjected to prenatal hypoxia (PH) and treated daily with physiological saline; and Groups 3 to 6—rat pups exposed to prenatal hypoxia and treated daily from the 1st to the 30th day after birth. Levels of sEPCR, Tie2 tyrosine kinase, VEGF-B, SOD1/Cu-Zn SOD, GPX4, and GPX1 in the heart’s cytosolic homogenate were assessed using ELISA. The expression of VEGF and VEGF-B mRNA was analyzed via real-time polymerase chain reaction, and the nuclear area of myocardial microvessel endothelial cells was evaluated morphometrically. <b>Results:</b> We have shown that only two representatives of this group—Angiolin and Thiotriazoline—are able to exert full effect on the indices of endothelial dysfunction after PH to decrease sEPCR, increase Tie-2, VEGF-B and VEGF-B mRNA, Cu/ZnSOD, and GPX in myocardial cytosol, and increase the area of endotheliocyte nuclei in 1- and 2-month-old rats in comparison with the control. <b>Conclusions:</b> Our results experimentally substantiate the necessity of early postnatal cardio- and endothelioprotection using NO modulators, taking into account the role of NO-dependent mechanisms in the pathogenesis of cardiovascular system disorders in neonates after PH.https://www.mdpi.com/1424-8247/18/1/106prenatal hypoxiacardioprotectiveendothelioprotectionNO systemangiolinL-arginine |
| spellingShingle | Igor Belenichev Olena Popazova Oleh Yadlovskyi Nina Bukhtiyarova Victor Ryzhenko Sergii Pavlov Valentyn Oksenych Oleksandr Kamyshnyi Possibility of Using NO Modulators for Pharmacocorrection of Endothelial Dysfunction After Prenatal Hypoxia Pharmaceuticals prenatal hypoxia cardioprotective endothelioprotection NO system angiolin L-arginine |
| title | Possibility of Using NO Modulators for Pharmacocorrection of Endothelial Dysfunction After Prenatal Hypoxia |
| title_full | Possibility of Using NO Modulators for Pharmacocorrection of Endothelial Dysfunction After Prenatal Hypoxia |
| title_fullStr | Possibility of Using NO Modulators for Pharmacocorrection of Endothelial Dysfunction After Prenatal Hypoxia |
| title_full_unstemmed | Possibility of Using NO Modulators for Pharmacocorrection of Endothelial Dysfunction After Prenatal Hypoxia |
| title_short | Possibility of Using NO Modulators for Pharmacocorrection of Endothelial Dysfunction After Prenatal Hypoxia |
| title_sort | possibility of using no modulators for pharmacocorrection of endothelial dysfunction after prenatal hypoxia |
| topic | prenatal hypoxia cardioprotective endothelioprotection NO system angiolin L-arginine |
| url | https://www.mdpi.com/1424-8247/18/1/106 |
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