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<article xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xmlns:ali="http://www.niso.org/schemas/ali/1.0/" article-type="research-article" dtd-version="1.2" xml:lang="ru"><front><journal-meta><journal-id journal-id-type="publisher-id">Russian Journal of Physiology</journal-id><journal-title-group><journal-title xml:lang="en">Russian Journal of Physiology</journal-title><trans-title-group xml:lang="ru"><trans-title>Российский физиологический журнал им. И.М. Сеченова</trans-title></trans-title-group></journal-title-group><issn publication-format="print">0869-8139</issn><issn publication-format="electronic">2658-655X</issn><publisher><publisher-name xml:lang="en">The Russian Academy of Sciences</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="publisher-id">651731</article-id><article-id pub-id-type="doi">10.31857/S0869813924100062</article-id><article-id pub-id-type="edn">VRPBFJ</article-id><article-categories><subj-group subj-group-type="toc-heading" xml:lang="en"><subject>EXPERIMENTAL ARTICLES</subject></subj-group><subj-group subj-group-type="toc-heading" xml:lang="ru"><subject>ЭКСПЕРИМЕНТАЛЬНЫЕ СТАТЬИ</subject></subj-group><subj-group subj-group-type="article-type"><subject>Research Article</subject></subj-group></article-categories><title-group><article-title xml:lang="en">Intrauterine growth restriction does not lead to pronounced changes in the regulation of arterial contractile responses in rats in the early postnatal period</article-title><trans-title-group xml:lang="ru"><trans-title>Задержка внутриутробного развития не приводит к выраженным изменениям в регуляции сократительных ответов артерий крыс в раннем постнатальном периоде</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author"><name-alternatives><name xml:lang="en"><surname>Shvetsova</surname><given-names>А. А.</given-names></name><name xml:lang="ru"><surname>Швецова</surname><given-names>А. А.</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><email>Dina.Gaynullina@gmail.com</email><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><name-alternatives><name xml:lang="en"><surname>Selivanova</surname><given-names>Е. К.</given-names></name><name xml:lang="ru"><surname>Селиванова</surname><given-names>Е. К.</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><email>Dina.Gaynullina@gmail.com</email><xref ref-type="aff" rid="aff1"/><xref ref-type="aff" rid="aff2"/></contrib><contrib contrib-type="author"><name-alternatives><name xml:lang="en"><surname>Shilova</surname><given-names>L. D.</given-names></name><name xml:lang="ru"><surname>Шилова</surname><given-names>Л. Д.</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><email>Dina.Gaynullina@gmail.com</email><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><name-alternatives><name xml:lang="en"><surname>Tarasova</surname><given-names>О. S.</given-names></name><name xml:lang="ru"><surname>Тарасова</surname><given-names>О. С.</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><email>Dina.Gaynullina@gmail.com</email><xref ref-type="aff" rid="aff1"/><xref ref-type="aff" rid="aff3"/></contrib><contrib contrib-type="author"><name-alternatives><name xml:lang="en"><surname>Gaynullina</surname><given-names>D. К.</given-names></name><name xml:lang="ru"><surname>Гайнуллина</surname><given-names>Д. К.</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><email>Dina.Gaynullina@gmail.com</email><xref ref-type="aff" rid="aff1"/></contrib></contrib-group><aff-alternatives id="aff1"><aff><institution xml:lang="en">Lomonosov Moscow State University</institution></aff><aff><institution xml:lang="ru">Московский государственный университет имени М. В. Ломоносова</institution></aff></aff-alternatives><aff-alternatives id="aff2"><aff><institution xml:lang="en">ChemRar Research and Development Institute</institution></aff><aff><institution xml:lang="ru">Научно-исследовательский институт «ХимРар»</institution></aff></aff-alternatives><aff-alternatives id="aff3"><aff><institution xml:lang="en">Institute of Biomedical Problems of the Russian Academy of Sciences</institution></aff><aff><institution xml:lang="ru">Государственный научный центр Российской Федерации – Институт медико-биологических проблем РАН</institution></aff></aff-alternatives><content-language>ru</content-language><pub-date date-type="pub" publication-format="electronic" iso-8601-date="2024-10-15"><day>15</day><month>10</month><year>2024</year></pub-date><pub-date date-type="collection"><year>2024</year></pub-date><volume>110</volume><issue>10</issue><issue-title xml:lang="ru"/><fpage>1652</fpage><lpage>1665</lpage><history><date date-type="received" iso-8601-date="2025-02-02"><day>02</day><month>02</month><year>2025</year></date></history><pub-history><event event-type="received"><event-desc>Received:<date date-type="received" iso-8601-date="2025-02-02"><day>02</day><month>02</month><year>2025</year></date></event-desc></event><event event-type="pub"><event-desc>Published:<pub-date date-type="pub" publication-format="electronic" iso-8601-date="2024-10-15"><day>15</day><month>10</month><year>2024</year></pub-date></event-desc></event></pub-history><permissions><copyright-statement xml:lang="en">Copyright ©; 2024, Russian Academy of Sciences</copyright-statement><copyright-statement xml:lang="ru">Copyright ©; 2024, Российская академия наук</copyright-statement><copyright-year>2024</copyright-year><copyright-holder xml:lang="en">Russian Academy of Sciences</copyright-holder><copyright-holder xml:lang="ru">Российская академия наук</copyright-holder></permissions><self-uri xlink:href="https://journals.eco-vector.com/0869-8139/article/view/651731">https://journals.eco-vector.com/0869-8139/article/view/651731</self-uri><abstract xml:lang="en"><p>Intrauterine growth retardation (IUGR) is one of the most common pathologies of pregnancy. As a result of this pathology, the functioning of many systems, including the cardiovascular system, is disrupted. In adult animals who have suffered IUGR, the contribution of procontractile mechanisms regulating vascular tone (for example, the Rho-kinase signaling pathway) increases, and the contribution of anticontractile mechanisms (for example, endothelial NO), on the contrary, decreases, which can lead to vasospasm and impaired blood supply to organs. Since NO and Rho-kinase have a pronounced vasomotor role in early postnatal ontogenesis, the purpose of this work was to assess the influence of IUGR on the contribution of these mechanisms to the regulation of arterial contractile responses in early postnatal ontogenesis. IUGR was modeled by limiting the amount of food consumed by females (by 50%) from the 11th day of pregnancy until birth. In offspring aged 11 - 12 days, the reactions of the isolated saphenous artery were studied in isometric mode, and the content of mRNA and proteins of interest in this artery was also assessed. IUGR did not lead to a change in the reactivity of the arteries of the offspring to the α1-adrenergic receptor agonist methoxamine. The increase in contractile responses to methoxamine in the presence of the NO-synthase inhibitor L-NNA, as well as the expression levels of eNOS (mRNA and protein) and arginase-2 (mRNA) were not changed in the arteries of IUGR rats, while the sensitivity of the arteries to the exogenous NO donor DEA /NO was higher in IUGR compared to control rat pups. Despite the relatively low content of RhoA and Rho-kinase II proteins in the arterial tissue of rat pups from the IUGR group, the decrease in contractile responses under the influence of the Rho-kinase inhibitor Y27632 was equally pronounced in the arteries of rat pups from two experimental groups. Thus, IUGR, caused by maternal nutritional restriction during pregnancy, does not lead to pronounced changes in the regulation of systemic vascular tone in the early postnatal period.</p></abstract><trans-abstract xml:lang="ru"><p>Задержка внутриутробного развития (ЗВУР) является одной из наиболее частых патологий беременности. В результате данной патологии нарушается функционирование многих систем, в том числе сердечно-сосудистой. У взрослых животных, перенесших ЗВУР, увеличивается вклад проконстрикторных механизмов регуляции сосудистого тонуса (например, сигнального пути Rho-киназы), а вклад антиконстрикторных механизмов (например, эндотелиального NO), напротив, уменьшается, что может приводить к спазмированию сосудов и нарушению кровоснабжения органов. Поскольку NO и Rho-киназа обладают ярко выраженной вазомоторной ролью в раннем постнатальном онтогенезе, целью данной работы стала оценка влияния ЗВУР на вклад этих механизмов в регуляцию сократительных ответов артерии системного кровообращения в раннем постнатальном онтогенезе. ЗВУР моделировали путем ограничения количества потребляемого самками корма (на 50%) с 11-го дня беременности до родов. У потомства в возрасте 11–12 дней исследовали реакции изолированной подкожной артерии в изометрическом режиме, а также оценивали содержание в этой артерии интересующих мРНК и белков. ЗВУР не привела к изменению реактивности артерий потомства на агонист α<sub>1</sub>-адренорецепторов метоксамин. Увеличение сократительных ответов на метоксамин в присутствии ингибитора NO-синтаз L-NNA, а также уровни экспрессии eNOS (мРНК и белка) и аргиназы-2 (мРНК) не были изменены в артериях крысят c ЗВУР, тогда как чувствительность артерий к экзогенному донору NO DEA/NO у них была выше, чем у контрольных крысят. Несмотря на сравнительно низкое содержание белков RhoA и Rho-киназы II в ткани артерий крысят группы ЗВУР, уменьшение сократительных ответов под действием ингибитора Rho-киназы Y27632 было одинаково выраженным в артериях крысят двух экспериментальных групп. Таким образом, ЗВУР, обусловленная ограничением питания матери во время беременности, не приводит к ярко выраженным изменениям в регуляции тонуса системных сосудов в раннем постнатальном периоде.</p></trans-abstract><kwd-group xml:lang="en"><kwd>intrauterine growth restriction</kwd><kwd>smooth muscle</kwd><kwd>endothelium</kwd><kwd>nitric oxide NO</kwd><kwd>Rho-kinase</kwd><kwd>early postnatal ontogenesis</kwd><kwd>artery</kwd></kwd-group><kwd-group xml:lang="ru"><kwd>задержка внутриутробного развития</kwd><kwd>артерии</kwd><kwd>гладкая мышца</kwd><kwd>эндотелий</kwd><kwd>оксид азота</kwd><kwd>Rho-киназа</kwd><kwd>ранний постнатальный онтогенез</kwd></kwd-group><funding-group><award-group><funding-source><institution-wrap><institution xml:lang="ru">Правительство Российской Федерации</institution></institution-wrap><institution-wrap><institution xml:lang="en">Government of the Russian Federation</institution></institution-wrap></funding-source><award-id>12586п-П8</award-id></award-group></funding-group></article-meta></front><body></body><back><ref-list><ref id="B1"><label>1.</label><mixed-citation>Yzydorczyk C, Armengaud JB, Peyter AC, Chehade H, Cachat F, Juvet C, Siddeek B, Simoncini S, Sabatier F, Dignat-George F, Mitanchez D, Simeoni U (2017) Endothelial dysfunction in individuals born after fetal growth restriction: cardiovascular and renal consequences and preventive approaches. J Dev Orig Health Dis 8: 448–464. https://doi.org/10.1017/S2040174417000265</mixed-citation></ref><ref id="B2"><label>2.</label><mixed-citation>Freije WA, Thamotharan S, Lee R, Shin B, Devaskar SU (2015) The Hepatic Transcriptome of Young Suckling and Aging Intrauterine Growth Restricted Male Rats. J Cell Biochem 116: 566–579. https://doi.org/10.1002/jcb.25008</mixed-citation></ref><ref id="B3"><label>3.</label><mixed-citation>Gibson LC, Shin B, Dai Y, Freije W, Kositamongkol S, Cho J, Devaskar SU (2015) Early leptin intervention reverses perturbed energy balance regulating hypothalamic neuropeptides in the pre‐ and postnatal calorie‐restricted female rat offspring. J Neurosci Res 93: 902–912. https://doi.org/10.1002/jnr.23560</mixed-citation></ref><ref id="B4"><label>4.</label><mixed-citation>Zanardo V, Visentin S, Trevisanuto D, Bertin M, Cavallin F, Cosmi E (2013) Fetal aortic wall thickness: a marker of hypertension in IUGR children? Hypertens Res 36: 440–443. https://doi.org/10.1038/hr.2012.219</mixed-citation></ref><ref id="B5"><label>5.</label><mixed-citation>Visentin S, Grumolato F, Battista G, Di B, Grisan E, Cosmi E (2014) Early origins of adult disease : Low birth weight and vascular remodeling. Atherosclerosis 237: 391–399. https://doi.org/10.1016/j.atherosclerosis.2014.09.027</mixed-citation></ref><ref id="B6"><label>6.</label><mixed-citation>Victora CG, Adair L, Fall C, Hallal PC, Martorell R, Richter L, Sachdev HS (2008) Maternal and Child Undernutrition: consequences for adult health and human capital. Lancet 371: 340–357. https://doi.org/10.1016/S0140-6736(07)61692-4</mixed-citation></ref><ref id="B7"><label>7.</label><mixed-citation>Torrens C, Brawley L, Anthony FW, Dance CS, Dunn R, Jackson AA, Poston L, Hanson MA (2006) Folate Supplementation During Pregnancy Improves Offspring Cardiovascular Dysfunction Induced by Protein Restriction. Hypertension 47: 982–987. https://doi.org/10.1161/01.HYP.0000215580.43711.d1</mixed-citation></ref><ref id="B8"><label>8.</label><mixed-citation>Franco M do C, Fortes ZB, Akamine EH, Kawamoto EM, Scavone C, De Britto LRG, Muscara MN, Teixeira SA, Tostes RCA, Carvalho MHC, Nigro D (2004) Tetrahydrobiopterin improves endothelial dysfunction and vascular oxidative stress in microvessels of intrauterine undernourished rats. J Physiol 558: 239–248. https://doi.org/10.1113/jphysiol.2004.064055</mixed-citation></ref><ref id="B9"><label>9.</label><mixed-citation>Oliveira V, de Souza LV, Fernandes T, Junior SDS, de Carvalho MHC, Akamine EH, Michelini LC, de Oliveira EM, Franco M do C (2017) Intrauterine growth restriction-induced deleterious adaptations in endothelial progenitor cells: possible mechanism to impair endothelial function. J Dev Orig Health Dis 8: 665–673. https://doi.org/10.1017/S2040174417000484</mixed-citation></ref><ref id="B10"><label>10.</label><mixed-citation>Torrens C, Brawley L, Barker AC, Itoh S, Poston L, Hanson MA (2003) Maternal protein restriction in the rat impairs resistance artery but not conduit artery function in pregnant offspring. J Physiol 547: 77–84. https://doi.org/10.1113/jphysiol.2002.026120</mixed-citation></ref><ref id="B11"><label>11.</label><mixed-citation>Rock CR, White TA, Piscopo BR, Sutherland AE, Pham Y, Camm EJ, Sehgal A, Polglase GR, Miller SL, Allison BJ (2023) Cardiovascular decline in offspring during the perinatal period in an ovine model of fetal growth restriction. Am J Physiol Hear Circ Physiol 325: H1266–H1278. https://doi.org/10.1152/ajpheart.00495.2023</mixed-citation></ref><ref id="B12"><label>12.</label><mixed-citation>Selivanova EK, Shvetsova AA, Shilova LD, Tarasova OS, Gaynullina DK (2021) Intrauterine growth restriction weakens anticontractile influence of NO in coronary arteries of adult rats. Sci Rep 11: 1–11. https://doi.org/10.1038/s41598-021-93491-3</mixed-citation></ref><ref id="B13"><label>13.</label><mixed-citation>Gaynullina DK, Schubert R, Tarasova OS (2019) Changes in endothelial nitric oxide production in systemic vessels during early ontogenesis – A key mechanism for the perinatal adaptation of the circulatory system. Int J Mol Sci 20: 1–12. https://doi.org/10.3390/ijms20061421</mixed-citation></ref><ref id="B14"><label>14.</label><mixed-citation>Gaynullina D, Lubomirov LT, Sofronova SI, Kalenchuk VU, Gloe T, Pfitzer G, Tarasova OS, Schubert R (2013) Functional remodelling of arterial endothelium during early postnatal development in rats. Cardiovasc Res 99: 612–621. https://doi.org/10.1093/cvr/cvt138</mixed-citation></ref><ref id="B15"><label>15.</label><mixed-citation>Sofronova SI, Borzykh AA, Gaynullina DK, Kuzmin IV, Shvetsova AA, Lukoshkova EV, Tarasova OS (2016) Endothelial nitric oxide weakens arterial contractile responses and reduces blood pressure during early postnatal development in rats. Nitric Oxide – Biol Chem 55–56: 1–9. https://doi.org/10.1016/j.niox.2016.02.005</mixed-citation></ref><ref id="B16"><label>16.</label><mixed-citation>Puzdrova VA, Kudryashova TV, Gaynullina DK, Mochalov SV, Aalkjaer C, Nilsson H, Vorotnikov AV, Schubert R, Tarasova OS (2014) Trophic action of sympathetic nerves reduces arterial smooth muscle Ca2+ sensitivity during early post-natal development in rats. Acta Physiol 212: 128–141. https://doi.org/10.1111/apha.12331</mixed-citation></ref><ref id="B17"><label>17.</label><mixed-citation>Mochalov SV, Tarasova NV, Kudryashova TV, Gaynullina DK, Kalenchuk VU, Borovik AS, Vorotnikov AV, Tarasova OS, Schubert R (2018) Higher Ca2+-sensitivity of arterial contraction in 1-week-old rats is due to a greater Rho-kinase activity. Acta Physiol 223: 1–15. https://doi.org/10.1111/apha.13044</mixed-citation></ref><ref id="B18"><label>18.</label><mixed-citation>Štulcová B (1977) Postnatal Development of Cardiac Output Distribution Measured by Radioactive Microspheres in Rats. Neonatology 32: 119–124. https://doi.org/10.1159/000241004</mixed-citation></ref><ref id="B19"><label>19.</label><mixed-citation>Mulvany MJ, Halpern W (1977) Contractile properties of small arterial resistance vessels in spontaneously hypertensive and normotensive rats. Circ Res 41: 19–26. https://doi.org/10.1161/01.RES.41.1.19</mixed-citation></ref><ref id="B20"><label>20.</label><mixed-citation>Тарасова ОС, Гайнуллина ДК (2017) Rho-киназа как ключевой участник регуляции тонуса сосудов в норме и при сосудистых расстройствах. Артер гипертен 23: 383–394. [Tarasova OS, Gainullina DK (2017) Rho-kinase as a key participant in the regulation of vascular tone in health and in vascular disorders. Arter hyperten 23: 383–394. (In Russ)]. https://doi.org/10.18705/1607-419X-2017-23-5-383-394</mixed-citation></ref><ref id="B21"><label>21.</label><mixed-citation>Garg M, Thamotharan M, Dai Y, Lagishetty V, Matveyenko AV, Lee WNP, Devaskar SU (2013) Glucose Intolerance and Lipid Metabolic Adaptations in Response to Intrauterine and Postnatal Calorie Restriction in Male Adult Rats. Endocrinology 154: 102–113. https://doi.org/10.1210/en.2012-1640</mixed-citation></ref><ref id="B22"><label>22.</label><mixed-citation>Garg M, Thamotharan M, Dai Y, Thamotharan S, Shin B, Stout D, Devaskar SU (2012) Early Postnatal Caloric Restriction Protects Adult Male Intrauterine Growth – Restricted Offspring From Obesity. Diabetes 61: 1391–1398. https://doi.org/10.2337/db11-1347</mixed-citation></ref><ref id="B23"><label>23.</label><mixed-citation>Thamotharan M, Shin B, Suddirikku DT, Thamotharan S, Garg M, Devaskar SU (2005) GLUT4 expression and subcellular localization in the intrauterine growth-restricted adult rat female offspring. Am J Physiol Metab 288: E935–E947. https://doi.org/10.1152/ajpendo.00342.2004</mixed-citation></ref><ref id="B24"><label>24.</label><mixed-citation>Zamojska J, Niewiadomska-Jarosik K, Kierzkowska B, Gruca M, Wosiak A, Smolewska E (2023) Lipid Profile in Children Born Small for Gestational Age. Nutrients 15. https://doi.org/10.3390/nu15224781</mixed-citation></ref><ref id="B25"><label>25.</label><mixed-citation>Brandes RP, Kim DY, Schmitz-Winnenthal FH, Amidi M, Gödecke A, Mülsch A, Busse R (2000) Increased nitrovasodilator sensitivity in endothelial nitric oxide synthase knockout mice: Role of soluble guanylyl cyclase. Hypertension 35: 231–236. https://doi.org/10.1161/01.hyp.35.1.231</mixed-citation></ref><ref id="B26"><label>26.</label><mixed-citation>Ohashi Y, Kawashima S, Hirata KI, Yamashita T, Ishida T, Inoue N, Sakoda T, Kurihara H, Yazaki Y, Yokoyama M (1998) Hypotension and reduced nitric oxide-elicited vasorelaxation in transgenic mice overexpressing endothelial nitric oxide synthase. J Clin Invest 102: 2061–2071. https://doi.org/10.1172/JCI4394</mixed-citation></ref><ref id="B27"><label>27.</label><mixed-citation>Krause BJ, Peñaloza E, Candia A, Cañas D, Hernández C, Arenas GA, Peralta-Scholz MJ, Valenzuela R, García-Herrera C, Herrera EA (2019) Adult vascular dysfunction in foetal growth-restricted guinea-pigs is associated with a neonate-adult switching in Nos3 DNA methylation. Acta Physiol 227: 1–13. https://doi.org/10.1111/apha.13328</mixed-citation></ref><ref id="B28"><label>28.</label><mixed-citation>Akopov SE, Zhang L, Pearce WJ (1998) Regulation of Ca2+ sensitization by PKC and rho proteins in ovine cerebral arteries: Effects of artery size and age. Am J Physiol Hear Circ Physiol 275: 930–939. https://doi.org/10.1152/ajpheart.1998.275.3.h930</mixed-citation></ref><ref id="B29"><label>29.</label><mixed-citation>Somlyo AP, Somlyo AV (2003) Ca2+ sensitivity of smooth muscle and nonmuscle myosin II: Modulated by G proteins, kinases, and myosin phosphatase. Physiol Rev 83: 1325–1358. https://doi.org/10.1152/physrev.00023.2003</mixed-citation></ref></ref-list></back></article>
