An Exogenous NO Donor Provokes Mechanical Alternans in Normal Rat Atria and Impairs Sarcomere Contractility in Right Atrial Cardiomyocytes in Atrial Fibrillation
Atrial fibrillation (AF) is the most common arrhythmia worldwide. AF is associated with a deficiency in nitric oxide (NO) production, which contributes to disturbances in the electrical and mechanical function of the atrial myocardium. NO donors are considered promising for the treatment and prevent...
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2025-05-01
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| author | Xenia Butova Tatiana Myachina Polina Mikhryakova Raisa Simonova Daniil Shchepkin Anastasia Khokhlova |
| author_facet | Xenia Butova Tatiana Myachina Polina Mikhryakova Raisa Simonova Daniil Shchepkin Anastasia Khokhlova |
| author_sort | Xenia Butova |
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| description | Atrial fibrillation (AF) is the most common arrhythmia worldwide. AF is associated with a deficiency in nitric oxide (NO) production, which contributes to disturbances in the electrical and mechanical function of the atrial myocardium. NO donors are considered promising for the treatment and prevention of AF, but their effects on atrial contractility are unclear. This study examines the direct impact of a low-molecular-weight NO donor, spermine-NONOate (NOC-22), on the contractile function of atrial cardiomyocytes in paroxysmal AF. To study whether an NO donor-induced increase in NO level causes chamber-specific changes in atrial contractility, we measured sarcomere length (SL) dynamics in contracting single cardiomyocytes from the rat left and right atria (LA, RA) using a 7-day acetylcholine-CaCl<sub>2</sub>-induced AF model. We showed that in control rats NOC-22 provoked alternans of sarcomere shortening in both LA and RA cardiomyocytes. In AF, NOC-22 decreased the sarcomere-shortening amplitudes and velocities of sarcomere shortening–relengthening and increased the magnitude of sarcomere-shortening alternans only in RA cardiomyocytes. The negative effects of NO donors on RA contractility warrant careful consideration of their use in AF treatment. |
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| institution | Kabale University |
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| language | English |
| publishDate | 2025-05-01 |
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| series | Biomolecules |
| spelling | doaj-art-ddc535d44e3345d6a513f6304e0d5ebc2025-08-20T03:47:53ZengMDPI AGBiomolecules2218-273X2025-05-0115573510.3390/biom15050735An Exogenous NO Donor Provokes Mechanical Alternans in Normal Rat Atria and Impairs Sarcomere Contractility in Right Atrial Cardiomyocytes in Atrial FibrillationXenia Butova0Tatiana Myachina1Polina Mikhryakova2Raisa Simonova3Daniil Shchepkin4Anastasia Khokhlova5Institute of Immunology and Physiology of the Ural Branch of the Russian Academy of Science, Pervomajskaya St. 106, Yekaterinburg 620078, RussiaInstitute of Immunology and Physiology of the Ural Branch of the Russian Academy of Science, Pervomajskaya St. 106, Yekaterinburg 620078, RussiaInstitute of Immunology and Physiology of the Ural Branch of the Russian Academy of Science, Pervomajskaya St. 106, Yekaterinburg 620078, RussiaInstitute of Immunology and Physiology of the Ural Branch of the Russian Academy of Science, Pervomajskaya St. 106, Yekaterinburg 620078, RussiaInstitute of Immunology and Physiology of the Ural Branch of the Russian Academy of Science, Pervomajskaya St. 106, Yekaterinburg 620078, RussiaDepartment of Biomedical Engineering, Washington University, 1 Brookings Drive, St. Louis, MO 63130-4899, USAAtrial fibrillation (AF) is the most common arrhythmia worldwide. AF is associated with a deficiency in nitric oxide (NO) production, which contributes to disturbances in the electrical and mechanical function of the atrial myocardium. NO donors are considered promising for the treatment and prevention of AF, but their effects on atrial contractility are unclear. This study examines the direct impact of a low-molecular-weight NO donor, spermine-NONOate (NOC-22), on the contractile function of atrial cardiomyocytes in paroxysmal AF. To study whether an NO donor-induced increase in NO level causes chamber-specific changes in atrial contractility, we measured sarcomere length (SL) dynamics in contracting single cardiomyocytes from the rat left and right atria (LA, RA) using a 7-day acetylcholine-CaCl<sub>2</sub>-induced AF model. We showed that in control rats NOC-22 provoked alternans of sarcomere shortening in both LA and RA cardiomyocytes. In AF, NOC-22 decreased the sarcomere-shortening amplitudes and velocities of sarcomere shortening–relengthening and increased the magnitude of sarcomere-shortening alternans only in RA cardiomyocytes. The negative effects of NO donors on RA contractility warrant careful consideration of their use in AF treatment.https://www.mdpi.com/2218-273X/15/5/735nitric oxideNO donoratrial fibrillationleft and right atriacardiomyocyte contractilitymechanical alternans |
| spellingShingle | Xenia Butova Tatiana Myachina Polina Mikhryakova Raisa Simonova Daniil Shchepkin Anastasia Khokhlova An Exogenous NO Donor Provokes Mechanical Alternans in Normal Rat Atria and Impairs Sarcomere Contractility in Right Atrial Cardiomyocytes in Atrial Fibrillation Biomolecules nitric oxide NO donor atrial fibrillation left and right atria cardiomyocyte contractility mechanical alternans |
| title | An Exogenous NO Donor Provokes Mechanical Alternans in Normal Rat Atria and Impairs Sarcomere Contractility in Right Atrial Cardiomyocytes in Atrial Fibrillation |
| title_full | An Exogenous NO Donor Provokes Mechanical Alternans in Normal Rat Atria and Impairs Sarcomere Contractility in Right Atrial Cardiomyocytes in Atrial Fibrillation |
| title_fullStr | An Exogenous NO Donor Provokes Mechanical Alternans in Normal Rat Atria and Impairs Sarcomere Contractility in Right Atrial Cardiomyocytes in Atrial Fibrillation |
| title_full_unstemmed | An Exogenous NO Donor Provokes Mechanical Alternans in Normal Rat Atria and Impairs Sarcomere Contractility in Right Atrial Cardiomyocytes in Atrial Fibrillation |
| title_short | An Exogenous NO Donor Provokes Mechanical Alternans in Normal Rat Atria and Impairs Sarcomere Contractility in Right Atrial Cardiomyocytes in Atrial Fibrillation |
| title_sort | exogenous no donor provokes mechanical alternans in normal rat atria and impairs sarcomere contractility in right atrial cardiomyocytes in atrial fibrillation |
| topic | nitric oxide NO donor atrial fibrillation left and right atria cardiomyocyte contractility mechanical alternans |
| url | https://www.mdpi.com/2218-273X/15/5/735 |
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