<?xml version="1.0" encoding="UTF-8"?>
<!DOCTYPE article PUBLIC "-//NLM//DTD JATS (Z39.96) Journal Publishing DTD v1.3 20210610//EN" "JATS-journalpublishing1-3.dtd">
<article article-type="research-article" dtd-version="1.3" 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" xml:lang="ru"><front><journal-meta><journal-id journal-id-type="publisher-id">r-n-j</journal-id><journal-title-group><journal-title xml:lang="ru">Российский неврологический журнал</journal-title><trans-title-group xml:lang="en"><trans-title>Russian neurological journal</trans-title></trans-title-group></journal-title-group><issn pub-type="ppub">2658-7947</issn><issn pub-type="epub">2686-7192</issn><publisher><publisher-name>МИА</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="doi">10.30629/2658-7947-2026-31-2-51-59</article-id><article-id custom-type="elpub" pub-id-type="custom">r-n-j-828</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="ru"><subject>ОБЗОРЫ</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="en"><subject>REVIEWS</subject></subj-group></article-categories><title-group><article-title>Асимметричный диметиларгинин как биохимический маркер дисфункции эндотелия при основных подтипах ишемического инсульта у мужчин трудоспособного возраста</article-title><trans-title-group xml:lang="en"><trans-title>Asymmetric dimethylarginine as a biochemical marker of endothelial dysfunction in major subtypes of ischemic stroke in working-age men</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-3009-3020</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Пизов</surname><given-names>Н. А.</given-names></name><name name-style="western" xml:lang="en"><surname>Pizov</surname><given-names>N. A.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Ярославль</p></bio><bio xml:lang="en"><p>Yaroslavl</p></bio><email xlink:type="simple">pizov.n.a@gmail.com</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-7465-0677</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Пизова</surname><given-names>Н. В.</given-names></name><name name-style="western" xml:lang="en"><surname>Pizova</surname><given-names>N. V.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Ярославль</p></bio><bio xml:lang="en"><p>Yaroslavl</p></bio><email xlink:type="simple">pizova@yandex.ru</email><xref ref-type="aff" rid="aff-2"/></contrib></contrib-group><aff-alternatives id="aff-1"><aff xml:lang="ru"><institution>Клиническая больница № 2</institution><country>Россия</country></aff><aff xml:lang="en"><institution>Clinical Hospital No.2</institution><country>Russian Federation</country></aff></aff-alternatives><aff-alternatives id="aff-2"><aff xml:lang="ru"><institution>Ярославский государственный медицинский университет</institution><country>Россия</country></aff><aff xml:lang="en"><institution>Yaroslavl State Medical University</institution><country>Russian Federation</country></aff></aff-alternatives><pub-date pub-type="collection"><year>2026</year></pub-date><pub-date pub-type="epub"><day>17</day><month>06</month><year>2026</year></pub-date><volume>31</volume><issue>2</issue><fpage>51</fpage><lpage>59</lpage><permissions><copyright-statement>Copyright &amp;#x00A9; Пизов Н.А., Пизова Н.В., 2026</copyright-statement><copyright-year>2026</copyright-year><copyright-holder xml:lang="ru">Пизов Н.А., Пизова Н.В.</copyright-holder><copyright-holder xml:lang="en">Pizov N.A., Pizova N.V.</copyright-holder><license xml:lang="ru" license-type="creative-commons-attribution" xlink:href="https://creativecommons.org/licenses/by/4.0/" xlink:type="simple"><license-p>Данная работа распространяется под лицензией Creative Commons Attribution 4.0.</license-p></license><license xml:lang="en" license-type="creative-commons-attribution" xlink:href="https://creativecommons.org/licenses/by/4.0/" xlink:type="simple"><license-p>This work is licensed under a Creative Commons Attribution 4.0 License.</license-p></license></permissions><self-uri xlink:href="https://www.r-n-j.com/jour/article/view/828">https://www.r-n-j.com/jour/article/view/828</self-uri><abstract><sec><title>Цель исследования</title><p>Цель исследования: определить уровень асимметричного диметиларгинина (АДМА) в плазме крови и оценить его роль в развитии эндотелиальной дисфункции при различных патогенетических подтипах инсульта у мужчин трудоспособного возраста (18–50 лет).</p></sec><sec><title>Материал и методы</title><p>Материал и методы. Исследование проведено на выборке из 125 больных мужчин в возрасте 18–50 лет (средний возраст составил 42,6 ± 5,3 года) с различными подтипами ишемического инсульта (ИИ), поступивших в неврологическое отделение в период до пандемии COVID-19. В исследование включено 60 пациентов с атеротромботическим инсультом (АТИ), 46 пациентов с лакунарным инсультом (ЛИ) и 19 пациентов с кардиоэмболическим инсультом (КЭИ). Подтип ИИ определялся на основании классификации TOAST. Были проведены оценка факторов риска, детальный соматический и неврологический осмотры, нейровизуализационное исследование головного мозга, ультразвуковое исследование магистральных артерий головы, лабораторное исследование.</p></sec><sec><title>Результаты</title><p>Результаты. У пациентов в возрасте 18–50 лет с различными подтипами ИИ выявлялись следующие факторы риска: артериальная гипертензия — в 83,2% случаев, дислипидемия — в 50,4%, сахарный диабет — в 8%, курение — в 67,2%, употребление алкоголя — в 29,6%, ожирение — в 16,8%, нарушение ритма сердца — в 12%, перенесенный инсульт в анамнезе — в 16,8%, перенесенный ранее острый инфаркт миокарда — в 10,4% случаев. АДМА был выше у пациентов с АТИ и с ЛИ по сравнению с пациентами с КЭИ. У пациентов с АТИ были самые высокие уровни АДМА. Пациенты с АТИ в возрасте 41–50 лет имели более высокие уровни АДМА по сравнению с пациентами в возрасте 31–40 лет. У пациентов с ЛИ и КЭИ более высокие уровни АДМА были в возрасте 31–40 лет по сравнению с пациентами в возрасте 41–50 лет. Выявлены значимые корреляции между уровнем АДМА и отдельными факторами риска при различных подтипах ИИ.</p></sec><sec><title>Заключение</title><p>Заключение. Изменения уровня АДМА связано с развитием и прогрессированием атеросклероза и эндотелиальной дисфункции у мужчин 18–50 лет с различными подтипами ИИ.</p></sec></abstract><trans-abstract xml:lang="en"><sec><title>The aim</title><p>The aim. To determine the level of ADMA in blood plasma and evaluate its role in the development of endothelial dysfunction in various pathogenetic subtypes of stroke in working-age men (18–50 years).</p></sec><sec><title>Material and methods</title><p>Material and methods. The study was conducted on a sample of 125 men (mean age 42.6 ± 5.3 years) with various subtypes of IS who were admitted to the neurological department before the COVID-19 pandemic. The study included 60 patients with atherothrombotic stroke (ATS), 46 patients with lacunar stroke (LS), and 19 patients with cardioembolic stroke (CES). The IS subtype was determined based on the TOAST classification (Trial of Org 10172 in Acute Stroke Treatment). The patients underwent risk factor assessment, detailed somatic and neurological examinations, neuroimaging of the brain, ultrasound examination of the main arteries of the head, and laboratory tests.</p></sec><sec><title>Results</title><p>Results. In men aged 18–50 years with various subtypes of IS, the following risk factors were identified: arterial hypertension in 83.2%, dyslipidemia in 50.4%, diabetes mellitus in 8%, smoking in 67.2%, alcohol consumption in 29.6%, obesity in 16.8%, cardiac arrhythmia in 12%, a history of stroke in 16.8%, and a history of acute myocardial infarction in 10.4%. In men aged 18–50, the level of ADMA was higher in patients with ATS and LS compared to patients with CES. Patients with ATS had the highest levels of ADMA. Patients with ATS aged 41–50 had higher levels of ADMA compared to patients aged 31–40. Patients with LS and CES had higher levels of ADMA at the age of 31–40 years compared to patients aged 41–50 years. Significant correlations were found between the level of ADMA and individual risk factors in different subtypes of IS.</p></sec><sec><title>Conclusion</title><p>Conclusion. The identified changes in the level of ADMA and the obtained correlation relationships reflect the role of ADMA in the development and progression of atherosclerosis and endothelial dysfunction in men aged 18–50 with various subtypes of IS.</p></sec></trans-abstract><kwd-group xml:lang="ru"><kwd>асимметричный диметиларгинин</kwd><kwd>эндотелиальная дисфункция</kwd><kwd>атеротромботический</kwd><kwd>лакунарный и кардиоэмболический подтипы ишемического инсульта</kwd><kwd>мужчины в возрасте 18–50 лет</kwd></kwd-group><kwd-group xml:lang="en"><kwd>asymmetric dimethylarginine</kwd><kwd>endothelial dysfunction</kwd><kwd>atherothrombotic</kwd><kwd>lacunar</kwd><kwd>and cardioembolic subtypes of ischemic stroke</kwd><kwd>men aged 18–50 years</kwd></kwd-group></article-meta></front><back><ref-list><title>References</title><ref id="cit1"><label>1</label><citation-alternatives><mixed-citation xml:lang="ru">Wang X, He B. Endothelial dysfunction: molecular mechanisms and clinical implications. MedComm. 2024;5(8):e651. doi: 10.1002/mco2.651.</mixed-citation><mixed-citation xml:lang="en">Wang X, He B. Endothelial dysfunction: molecular mechanisms and clinical implications. MedComm. 2024;5(8):e651. doi: 10.1002/mco2.651.</mixed-citation></citation-alternatives></ref><ref id="cit2"><label>2</label><citation-alternatives><mixed-citation xml:lang="ru">Tuttolomondo A Daidone M Pinto A. Endothelial dysfunction and inflammation in ischemic stroke pathogenesis. Curr Pharm Des. 2020;26(34):4209–4219. doi: 10.2174/1381612826666200417154126</mixed-citation><mixed-citation xml:lang="en">Tuttolomondo A Daidone M Pinto A. Endothelial dysfunction and infl ammation in ischemic stroke pathogenesis. Curr Pharm Des. 2020;26(34):4209–4219. doi: 10.2174/1381612826666200417154126</mixed-citation></citation-alternatives></ref><ref id="cit3"><label>3</label><citation-alternatives><mixed-citation xml:lang="ru">Iadecola C. The neurovascular unit coming of age: a journey through neurovascular coupling in health and disease. Neuron. 2017;96(1):17–42. doi: 10.1016/j.neuron.2017.07.030</mixed-citation><mixed-citation xml:lang="en">Iadecola C. The neurovascular unit coming of age: a journey through neurovascular coupling in health and disease. Neuron. 2017;96(1):17–42. doi: 10.1016/j.neuron.2017.07.030</mixed-citation></citation-alternatives></ref><ref id="cit4"><label>4</label><citation-alternatives><mixed-citation xml:lang="ru">Madden JA. Role of the vascular endothelium and plaque in acute ischemic stroke. Neurology. 2012;79(13 Suppl1):S58-62. doi: 10.1212/WNL.0b013e3182695836</mixed-citation><mixed-citation xml:lang="en">Madden JA. Role of the vascular endothelium and plaque in acute ischemic stroke. Neurology. 2012;79(13 Suppl1):S58-62. doi: 10.1212/WNL.0b013e3182695836</mixed-citation></citation-alternatives></ref><ref id="cit5"><label>5</label><citation-alternatives><mixed-citation xml:lang="ru">Poggesi A, Pasi M, Pescini F, Pantoni L, Inzitari D. Circulating biologic markers of endothelial dysfunction in cerebral small vessel disease: a review. J Cereb Blood Flow Metab. 2016;36(1):72–94. doi: 10.1038/jcbfm.2015.116.</mixed-citation><mixed-citation xml:lang="en">Poggesi A, Pasi M, Pescini F, Pantoni L, Inzitari D. Circulating biologic markers of endothelial dysfunction in cerebral small vessel disease: a review. J Cereb Blood Flow Metab. 2016;36(1):72– 94. doi: 10.1038/jcbfm.2015.116.</mixed-citation></citation-alternatives></ref><ref id="cit6"><label>6</label><citation-alternatives><mixed-citation xml:lang="ru">Zhang J. Biomarkers of endothelial activation and dysfunction in cardiovascular diseases. Rev Cardiovasc Med. 2022;23(2):73. doi: 10.31083/j.rcm2302073.</mixed-citation><mixed-citation xml:lang="en">Zhang J. Biomarkers of endothelial activation and dysfunction in cardiovascular diseases. Rev Cardiovasc Med. 2022;23(2):73. doi: 10.31083/j.rcm2302073.</mixed-citation></citation-alternatives></ref><ref id="cit7"><label>7</label><citation-alternatives><mixed-citation xml:lang="ru">Adams HP, Bendixen BH, Kappelle LJ, Biller J, Love BB, Gordon DL, Marsh 3rd E.E. Classification of subtype of acute ischemic stroke definitions for use in a multicenter clinical trial. Stroke. 1993;24(1):35–41. doi: 10.1161/01.str.24.1.35</mixed-citation><mixed-citation xml:lang="en">Adams HP, Bendixen BH, Kappelle LJ, Biller J, Love BB, Gordon DL, Marsh 3rd E.E. Classifi cation of subtype of acute ischemic stroke defi nitions for use in a multicenter clinical trial. Stroke. 1993;24(1):35–41. doi: 10.1161/01.str.24.1.35</mixed-citation></citation-alternatives></ref><ref id="cit8"><label>8</label><citation-alternatives><mixed-citation xml:lang="ru">Celermajer DS, Sorensen KE, Gooch VM, Spiegelhalter DJ, Miller OI, Sullivan ID, Lloyd JK, Deanfield JE. Non-invasive detection of endothelial dysfunction in children and adults at risk of atherosclerosis. Lancet. 1992;340:1111–1115. doi: 10.1016/0140-6736(92)93147-F</mixed-citation><mixed-citation xml:lang="en">Celermajer DS, Sorensen KE, Gooch VM, Spiegelhalter DJ, Miller OI, Sullivan ID, Lloyd JK, Deanfi eld JE. Non-invasive detection of endothelial dysfunction in children and adults at risk of atherosclerosis. Lancet. 1992;340:1111–1115. doi: 10.1016/0140-6736(92)93147-F</mixed-citation></citation-alternatives></ref><ref id="cit9"><label>9</label><citation-alternatives><mixed-citation xml:lang="ru">Бокерия ЛА, Бокерия ОЛ, Базарсадаева ТС, Салия НТ, Донаканян СА, Биниашвили МБ, Таскина ВЮ. Характеристика NO-зависимой ауторегуляции тканевого кровотока при идиопатической фибрилляции предсердий. Анналы аритмологии. 2013;10(2):94–101.</mixed-citation><mixed-citation xml:lang="en">Bokeria LA, Bokeria OL, Bazar-Sadaeva TS, Salia NT, Donakanyan SA, Binia-Shvili MB, Taskina V.Yu. Characteristics of NO-dependent autoregulation of tissue blood fl ow in idiopathic atrial fi brillation. Annaly aritmologii. 2013;10(2):94–101. (In Russ.). https://cyberleninka.ru/article/n/harakteristika-no-zavisimoy-autoregulyatsii-tkanevogo-krovotoka-pri-idiopaticheskoyfibrillyatsii-predserdiy?ysclid=mjr8av6t8f832382920</mixed-citation></citation-alternatives></ref><ref id="cit10"><label>10</label><citation-alternatives><mixed-citation xml:lang="ru">Прибылова НН, Беззубцева МВ, Прибылов СА, Барбашина ТА, Осипова ОА. Эндотелиальная дисфункция у больных гипертонической болезнью в остром периоде ишемического инсульта. Трудный пациент. 2016;6-7:14:17–20.</mixed-citation><mixed-citation xml:lang="en">Pribylova NN, Bezzubtseva MV, Pribylov SA, Barbashina TA, Osipova OA. Endothelial Dysfunction in Patients with Arterial Hypertension and AcuteIschemic Stroke. Trudnyi-Patsient. 2016;6-7:14:17–20. (In Russ.). https://cyberleninka.ru/article/n/endotelialnaya-disfunktsiya-u-bolnyh-gipertonicheskoy-boleznyu-v-ostrom-periode-ishemicheskogo-insulta?ysclid=mjr89w8hyu953350724</mixed-citation></citation-alternatives></ref><ref id="cit11"><label>11</label><citation-alternatives><mixed-citation xml:lang="ru">Alexander Y, Osto E, Schmidt-Trucksäss A, Shechter M, Trifunovic D, Duncker DJ, Aboyans V, Bäck M, Badimon L, Cosentino F, De Carlo M, Dorobantu M, Harrison DG, Guzik TJ, Hoefer I, Morris PD, Norata GD, Suades R, Taddei S, Vilahur G, Waltenberger J, Weber C, Wilkinson F, Bochaton-Piallat M-L., Evans PC. Endothelial function in cardiovascular medicine: a consensus paper of the European Society of Cardiology Working Groups on Atherosclerosis and Vascular Biology, Aorta and Peripheral Vascular Diseases, Coronary Pathophysiology and Microcirculation, and Thrombosis. Cardiovasc Res. 2021;117(1):29–42. doi: 10.1093/cvr/cvaa085</mixed-citation><mixed-citation xml:lang="en">Alexander Y, Osto E, Schmidt-Trucksäss A, Shechter M, Trifunovic D, Duncker DJ, Aboyans V, Bäck M, Badimon L, Cosentino F, De Carlo M, Dorobantu M, Harrison DG, Guzik TJ, Hoefer I, Morris PD, Norata GD, Suades R, Taddei S, Vilahur G, Waltenberger J, Weber C, Wilkinson F, Bochaton-Piallat M-L., Evans PC. Endothelial function in cardiovascular medicine: a consensus paper of the European Society of Cardiology Working Groups on Atherosclerosis and Vascular Biology, Aorta and Peripheral Vascular Diseases, Coronary Pathophysiology and Microcirculation, and Thrombosis. Cardiovasc Res. 2021;117(1):29–42. doi: 10.1093/cvr/cvaa085</mixed-citation></citation-alternatives></ref><ref id="cit12"><label>12</label><citation-alternatives><mixed-citation xml:lang="ru">George MG. Risk Factors for Ischemic Stroke in Younger Adults: A Focused Update. Stroke. 2020;51(3):729–735. doi: 10.1161/STROKEAHA.119.024156</mixed-citation><mixed-citation xml:lang="en">George MG. Risk Factors for Ischemic Stroke in Younger Adults: A Focused Update. Stroke. 2020;51(3):729–735. doi: 10.1161/STROKEAHA.119.024156</mixed-citation></citation-alternatives></ref><ref id="cit13"><label>13</label><citation-alternatives><mixed-citation xml:lang="ru">Hauer AJ, Ruigrok YM, Algra A, Dijk EJ, Koudstaal PJ, Luijckx GJ, Nederkoorn PJ, Oostenbrugge RJ, Visser MC, Wermer MJ, Kappelle LJ, Klijn CJ.M.; Dutch Parelsnoer Institute‐Cerebrovascular Accident Study Group. Age‐specific vascular risk factor profiles according to stroke subtype. J Am Heart Assoc. 2017;6:e005090. doi: 10.1161/JAHA.116.005090</mixed-citation><mixed-citation xml:lang="en">Hauer AJ, Ruigrok YM, Algra A, Dijk EJ, Koudstaal PJ, Luijckx GJ, Nederkoorn PJ, Oostenbrugge RJ, Visser MC, Wermer MJ, Kappelle LJ, Klijn CJ.M.; Dutch Parelsnoer Institute‐Cerebrovascular Accident Study Group. Age‐specifi c vascular risk factor profi les according to stroke subtype. J Am Heart Assoc. 2017;6:e005090. doi: 10.1161/JAHA.116.005090</mixed-citation></citation-alternatives></ref><ref id="cit14"><label>14</label><citation-alternatives><mixed-citation xml:lang="ru">Dittrich TD, Schneider T, Katan M, Luft AR, Mono ML, Bolognese M, Nedeltchev K, Kahles T, Arnold M, Heldner M, Michel P, Carrera E, Rodic B, Cereda CW, Peters N, Bonati LH, Renaud S, Humm AM, Medlin F, Albert S, Sturzenegger R, Tarnutzer AA, Siebel P, Baumgärtner M, Berger C, Mordasini P, Vehoff J, De Marchis GM.; Swiss Stroke Registry Investigators. Risk Factors, Treatments, and Outcomes of Adults Aged &lt; 55 Years With Acute Ischemic Stroke With Undetermined Versus Determined Pathogenesis: A Nationwide Swiss Cohort Study. J Am Heart Assoc. 2024;13(23):e036761. doi: 10.1161/JAHA.124.036761</mixed-citation><mixed-citation xml:lang="en">Dittrich TD, Schneider T, Katan M, Luft AR, Mono ML, Bolognese M, Nedeltchev K, Kahles T, Arnold M, Heldner M, Michel P, Carrera E, Rodic B, Cereda CW, Peters N, Bonati LH, Renaud S, Humm AM, Medlin F, Albert S, Sturzenegger R, Tarnutzer AA, Siebel P, Baumgärtner M, Berger C, Mordasini P, Vehoff  J, De Marchis GM.; Swiss Stroke Registry Investigators. Risk Factors, Treatments, and Outcomes of Adults Aged &lt; 55 Years With Acute Ischemic Stroke With Undetermined Versus Determined Pathogenesis: A Nationwide Swiss Cohort Study. J Am Heart Assoc. 2024;13(23):e036761. doi: 10.1161/JAHA.124.036761</mixed-citation></citation-alternatives></ref><ref id="cit15"><label>15</label><citation-alternatives><mixed-citation xml:lang="ru">Gerdanovics A, Stănescu IC, Mîrza CM, Dogaru GB, Nicula CA, Boarescu PM, Gerdanovics CA, Bulboacă AE. Proinflammatory Risk Factors in Patients with Ischemic Stroke: A Systematic Review and Meta-Analysis. Antioxidants (Basel). 2025;14(10):1229. doi: 10.3390/antiox14101229</mixed-citation><mixed-citation xml:lang="en">Gerdanovics A, Stănescu IC, Mîrza CM, Dogaru GB, Nicula CA, Boarescu PM, Gerdanovics CA, Bulboacă AE. Proinfl ammatory Risk Factors in Patients with Ischemic Stroke: A Systematic Review and Meta-Analysis. Antioxidants (Basel). 2025;14(10):1229. doi: 10.3390/antiox14101229</mixed-citation></citation-alternatives></ref><ref id="cit16"><label>16</label><citation-alternatives><mixed-citation xml:lang="ru">Tohgi H, Tajima T, Konno T, Towada S, Kamata A, Yamazaki M. The risk of cerebral infarction in non-valvular atrial fibrillation: Effects of age, hypertension and antihypertensive treatment. Eur. Neurol. 1991;31:126–130. doi: 10.1159/000116661</mixed-citation><mixed-citation xml:lang="en">Tohgi H, Tajima T, Konno T, Towada S, Kamata A, Yamazaki M. The risk of cerebral infarction in non-valvular atrial fi brillation: Eff ects of age, hypertension and antihypertensive treatment. Eur. Neurol. 1991;31:126–130. doi: 10.1159/000116661</mixed-citation></citation-alternatives></ref><ref id="cit17"><label>17</label><citation-alternatives><mixed-citation xml:lang="ru">Park JH, Ovbiagele B, Hong KS, Kwon SU. Association of Systolic Blood Pressure with Progression of Symptomatic Intracranial Atherosclerotic Stenosis. J. Stroke. 2017;19:304–311. doi: 10.5853/jos.2017.00136.</mixed-citation><mixed-citation xml:lang="en">Park JH, Ovbiagele B, Hong KS, Kwon SU. Association of Systolic Blood Pressure with Progression of Symptomatic Intracranial Atherosclerotic Stenosis. J. Stroke. 2017;19:304–311. doi: 10.5853/jos.2017.00136.</mixed-citation></citation-alternatives></ref><ref id="cit18"><label>18</label><citation-alternatives><mixed-citation xml:lang="ru">Kozera GM, Dubaniewicz M, Zdrojewski T, Madej-Dmochowska A, Mielczarek M, Wojczal J, Chwojnicki K, Swierblewska E, Schminke U, Wyrzykowski B, Nyka WM.; SOPKARD Study Group. Cerebral vasomotor reactivity and extent of white matter lesions in middle-aged men with arterial hypertension: A pilot study. Am. J. Hypertens. 2010;23:1198–1203. doi: 10.1038/ajh.2010.152</mixed-citation><mixed-citation xml:lang="en">Kozera GM, Dubaniewicz M, Zdrojewski T, Madej-Dmochowska A, Mielczarek M, Wojczal J, Chwojnicki K, Swierblewska E, Schminke U, Wyrzykowski B, Nyka WM.; SOPKARD Study Group. Cerebral vasomotor reactivity and extent of white matter lesions in middle-aged men with arterial hypertension: A pilot study. Am. J. Hypertens. 2010;23:1198–1203. doi: 10.1038/ajh.2010.152</mixed-citation></citation-alternatives></ref><ref id="cit19"><label>19</label><citation-alternatives><mixed-citation xml:lang="ru">Rundek T, Hundle R, Ratchford E, Ramas R, Sciacca R, Di Tullio MR, Boden-Albala B, Miyake Y, Elkind MS.V., Sacco RL, Homma S. Endothelial dysfunction is associated with carotid plaque: A cross-sectional study from the population based Northern Manhattan Study. BMC Cardiovasc. Disord. 2006;6:35. doi: 10.1186/1471-2261-6-35</mixed-citation><mixed-citation xml:lang="en">Rundek T, Hundle R, Ratchford E, Ramas R, Sciacca R, Di Tullio MR, Boden-Albala B, Miyake Y, Elkind MS.V., Sacco RL, Homma S. Endothelial dysfunction is associated with carotid plaque: A cross-sectional study from the population based Northern Manhattan Study. BMC Cardiovasc. Disord. 2006;6:35. doi: 10.1186/1471-2261-6-35</mixed-citation></citation-alternatives></ref><ref id="cit20"><label>20</label><citation-alternatives><mixed-citation xml:lang="ru">Knottnerus IL.H., Ten Cate H, Lodder J, Kessels F, van Oostenbrugge RJ. Endothelial dysfunction in lacunar stroke: A systematic review. Cerebrovasc. Dis. 2009;27:519–526. doi: 10.1159/000212672</mixed-citation><mixed-citation xml:lang="en">Knottnerus IL.H., Ten Cate H, Lodder J, Kessels F, van Oostenbrugge RJ. Endothelial dysfunction in lacunar stroke: A systematic review. Cerebrovasc. Dis. 2009;27:519–526. doi: 10.1159/000212672</mixed-citation></citation-alternatives></ref><ref id="cit21"><label>21</label><citation-alternatives><mixed-citation xml:lang="ru">Stevenson SF, Doubal FN, Shuler K, Wardlaw JM. A Systematic Review of Dynamic Cerebral and Peripheral Endothelial Function in Lacunar Stroke Versus Controls. Stroke. 2010;41:e434–e442. doi: 10.1161/STROKEAHA.109.569855</mixed-citation><mixed-citation xml:lang="en">Stevenson SF, Doubal FN, Shuler K, Wardlaw JM. A Systematic Review of Dynamic Cerebral and Peripheral Endothelial Function in Lacunar Stroke Versus Controls. Stroke. 2010;41:e434–e442. doi: 10.1161/STROKEAHA.109.569855</mixed-citation></citation-alternatives></ref><ref id="cit22"><label>22</label><citation-alternatives><mixed-citation xml:lang="ru">Micieli G, Bosone D, Zappoli F, Marcheselli S, Argenteri A, Nappi G. Vasomotor response to CO2 and L-Arginine in patients with severe internal carotid artery stenosis; pre- and postsurgical evaluation with transcranial Doppler. J. Neurol. Sci. 1999;163:153–158. doi: 10.1016/S0022-510X(99)00027-1</mixed-citation><mixed-citation xml:lang="en">Micieli G, Bosone D, Zappoli F, Marcheselli S, Argenteri A, Nappi G. Vasomotor response to CO2 and L-Arginine in patients with severe internal carotid artery stenosis; pre- and postsurgical evaluation with transcranial Doppler. J. Neurol. Sci. 1999;163:153–158. doi: 10.1016/S0022-510X(99)00027-1</mixed-citation></citation-alternatives></ref><ref id="cit23"><label>23</label><citation-alternatives><mixed-citation xml:lang="ru">Wieczór AM, Wieczór R, Kulwas A, Rość D. Asymmetric dimethylarginine and angiogenesis: biological significance. Int Angiol. 2018c;37(6):431–436. doi: 10.23736/S0392-9590.18.04017-8</mixed-citation><mixed-citation xml:lang="en">Wieczór AM, Wieczór R, Kulwas A, Rość D. Asymmetric dimethylarginine and angiogenesis: biological signifi cance. Int Angiol. 2018c;37(6):431–436. doi: 10.23736/S0392-9590.18.04017-8</mixed-citation></citation-alternatives></ref><ref id="cit24"><label>24</label><citation-alternatives><mixed-citation xml:lang="ru">Kielstein JT, Zoccali C. Asymmetric dimethylarginine: a cardiovascular risk factor and a uremic toxin coming of age? Am J Kidney Dis. 2005;46(2):186–202. doi: 10.1053/j.ajkd.2005.05.009</mixed-citation><mixed-citation xml:lang="en">Kielstein JT, Zoccali C. Asymmetric dimethylarginine: a cardiovascular risk factor and a uremic toxin coming of age? Am J Kidney Dis. 2005;46(2):186–202. doi: 10.1053/j.ajkd.2005.05.009</mixed-citation></citation-alternatives></ref><ref id="cit25"><label>25</label><citation-alternatives><mixed-citation xml:lang="ru">Goonasekera CD, Rees DD, Woolard P, Frend A, Shah V, Dillon MJ. Nitric oxide synthase inhibitors and hypertension in children and adolescents. J Hypertens. 1997;15(8):901–9. doi: 10.1097/00004872-199715080-00015</mixed-citation><mixed-citation xml:lang="en">Goonasekera CD, Rees DD, Woolard P, Frend A, Shah V, Dillon MJ. Nitric oxide synthase inhibitors and hypertension in children and adolescents. J Hypertens. 1997;15(8):901–9. doi: 10.1097/00004872-199715080-00015</mixed-citation></citation-alternatives></ref><ref id="cit26"><label>26</label><citation-alternatives><mixed-citation xml:lang="ru">Chirinos JA, David R, Bralley JA, Zea-Díaz H, Muñoz-Atahualpa E, Corrales-Medina F, Cuba-Bustinza C, Chirinos-Pacheco J, Medina-Lezama J. Endogenous nitric oxide synthase inhibitors, arterial hemodynamics, and subclinical vascular disease: the PREVENCION study. Hypertension. 2008;52(6):1051–9. doi: 10.1161/HYPERTENSIONAHA.108.120352</mixed-citation><mixed-citation xml:lang="en">Chirinos JA, David R, Bralley JA, Zea-Díaz H, Muñoz-Atahualpa E, Corrales-Medina F, Cuba-Bustinza C, Chirinos-Pacheco J, Medina-Lezama J. Endogenous nitric oxide synthase inhibitors, arterial hemodynamics, and subclinical vascular disease: the PREVENCION study. Hypertension. 2008;52(6):1051–9. doi: 10.1161/HYPERTENSIONAHA.108.120352</mixed-citation></citation-alternatives></ref><ref id="cit27"><label>27</label><citation-alternatives><mixed-citation xml:lang="ru">Schulze F, Lenzen H, Hanefeld C, Bartling A, Osterziel KJ, Goudeva L, Schmidt-Lucke C, Kusus M, Maas R, Schwedhelm E, Strödter D, Simon BC, Mügge A, Daniel WG, Tillmanns H, Maisch D, Streichert T, Böger RH. Asymmetric dimethylarginine is an independent risk factor for coronary heart disease: results from the multicenter Coronary Artery Risk Determination investigating the Influence of ADMA Concentration (CARDIAC) study. Am Heart J. 2006;152(3):493.e1-8. doi: 10.1016/j.ahj.2006.06.005</mixed-citation><mixed-citation xml:lang="en">Schulze F, Lenzen H, Hanefeld C, Bartling A, Osterziel KJ, Goudeva L, Schmidt-Lucke C, Kusus M, Maas R, Schwedhelm E, Strödter D, Simon BC, Mügge A, Daniel WG, Tillmanns H, Maisch D, Streichert T, Böger RH. Asymmetric dimethylarginine is an independent risk factor for coronary heart disease: results from the multicenter Coronary Artery Risk Determination investigating the Infl uence of ADMA Concentration (CARDIAC) study. Am Heart J. 2006;152(3):493.e1-8. doi: 10.1016/j.ahj.2006.06.005</mixed-citation></citation-alternatives></ref><ref id="cit28"><label>28</label><citation-alternatives><mixed-citation xml:lang="ru">Cooke JP. Asymmetrical dimethylarginine: the Uber marker? Circulation. 2004;109(15):1813–8. doi: 10.1161/01.CIR.0000126823.07732.D5</mixed-citation><mixed-citation xml:lang="en">Cooke JP. Asymmetrical dimethylarginine: the Uber marker? Circulation. 2004;109(15):1813–8. doi: 10.1161/01.CIR.0000126823.07732.D5</mixed-citation></citation-alternatives></ref><ref id="cit29"><label>29</label><citation-alternatives><mixed-citation xml:lang="ru">Horowitz JD, Heresztyn, T. An overview of plasma concentrations of asymmetric dimethylarginine (ADMA) in health and disease and in clinical studies: methodological considerations. J Chromatogr B Analyt Technol Biomed Life Sci. 2007;851(12):42–50. doi: 10.1016/j.jchromb.2006.09.023</mixed-citation><mixed-citation xml:lang="en">Horowitz JD, Heresztyn, T. An overview of plasma concentrations of asymmetric dimethylarginine (ADMA) in health and disease and in clinical studies: methodological considerations. J Chromatogr B Analyt Technol Biomed Life Sci. 2007;851(12):42–50. doi: 10.1016/j.jchromb.2006.09.023</mixed-citation></citation-alternatives></ref><ref id="cit30"><label>30</label><citation-alternatives><mixed-citation xml:lang="ru">Chauhan A, More RS, Mullins PA, Taylor G, Petch C, Schofield PM. Aging-associated endothelial dysfunction in humans is reversed by L-arginine. J Am Coll Cardiol. 1996;28(7):1796–804. doi: 10.1016/s0735-1097(96)00394-4</mixed-citation><mixed-citation xml:lang="en">Chauhan A, More RS, Mullins PA, Taylor G, Petch C, Schofi eld PM. Aging-associated endothelial dysfunction in humans is reversed by L-arginine. J Am Coll Cardiol. 1996;28(7):1796–804. doi: 10.1016/s0735-1097(96)00394-4</mixed-citation></citation-alternatives></ref><ref id="cit31"><label>31</label><citation-alternatives><mixed-citation xml:lang="ru">Bladowski M, Gawrys J, Gajecki D, Szahidewicz-Krupska E, Sawicz-Bladowska A, Doroszko A. Role of the Platelets and Nitric Oxide Biotransformation in Ischemic Stroke: A Translative Review from Bench to Bedside. Oxid Med Cell Longev. 2020;2020:2979260. doi: 10.1155/2020/2979260</mixed-citation><mixed-citation xml:lang="en">Bladowski M, Gawrys J, Gajecki D, Szahidewicz-Krupska E, Sawicz-Bladowska A, Doroszko A. Role of the Platelets and Nitric Oxide Biotransformation in Ischemic Stroke: A Translative Review from Bench to Bedside. Oxid Med Cell Longev. 2020;2020:2979260. doi: 10.1155/2020/2979260</mixed-citation></citation-alternatives></ref><ref id="cit32"><label>32</label><citation-alternatives><mixed-citation xml:lang="ru">Jacobsen JC.B., Hornbech MS, Holstein-Rathlou N.-H. Significance of microvascular remodelling for the vascular flow reserve in hypertension. Interface Focus. 2011;1:117–131. doi: 10.1098/rsfs.2010.0003</mixed-citation><mixed-citation xml:lang="en">Jacobsen JC.B., Hornbech MS, Holstein-Rathlou N.-H. Signifi cance of microvascular remodelling for the vascular fl ow reserve in hypertension. Interface Focus. 2011;1:117–131. doi: 10.1098/rsfs.2010.0003</mixed-citation></citation-alternatives></ref><ref id="cit33"><label>33</label><citation-alternatives><mixed-citation xml:lang="ru">Konukoglu D, Uzun H. Endothelial Dysfunction and Hypertension. Adv. Exp. Med. Biol. 2017;956:511–540. doi: 10.1007/5584_2016_90</mixed-citation><mixed-citation xml:lang="en">Konukoglu D, Uzun H. Endothelial Dysfunction and Hypertension. Adv. Exp. Med. Biol. 2017;956:511–540. doi: 10.1007/5584_2016_90</mixed-citation></citation-alternatives></ref><ref id="cit34"><label>34</label><citation-alternatives><mixed-citation xml:lang="ru">Li S, Wu Y, Yu G, Xia Q, Xu Y. Angiotensin II Receptor Blockers Improve Peripheral Endothelial Function: A Meta-Analysis of Randomized Controlled Trials. PLoS ONE. 2014;9:e90217. doi: 10.1371/journal.pone.0090217</mixed-citation><mixed-citation xml:lang="en">Li S, Wu Y, Yu G, Xia Q, Xu Y. Angiotensin II Receptor Blockers Improve Peripheral Endothelial Function: A Meta-Analysis of Randomized Controlled Trials. PLoS ONE. 2014;9:e90217. doi: 10.1371/journal.pone.0090217</mixed-citation></citation-alternatives></ref><ref id="cit35"><label>35</label><citation-alternatives><mixed-citation xml:lang="ru">Shahin Y, Alam Khan J, Samuel N, Chetter I. Angiotensin converting enzyme inhibitors effect on endothelial dysfunction: A meta-analysis of randomised controlled trials. Atherosclerosis. 2011;216:7–16. doi: 10.1016/j.atherosclerosis.2011.02.044</mixed-citation><mixed-citation xml:lang="en">Shahin Y, Alam Khan J, Samuel N, Chetter I. Angiotensin converting enzyme inhibitors eff ect on endothelial dysfunction: A meta-analysis of randomised controlled trials. Atherosclerosis. 2011;216:7–16. doi: 10.1016/j.atherosclerosis.2011.02.044</mixed-citation></citation-alternatives></ref><ref id="cit36"><label>36</label><citation-alternatives><mixed-citation xml:lang="ru">Golbidi S, Edvinsson L, Laher I. Smoking and Endothelial Dysfunction. Curr. Vasc. Pharmacol. 2020;18:1–11. doi: 10.2174/1573403X14666180913120015</mixed-citation><mixed-citation xml:lang="en">Golbidi S, Edvinsson L, Laher I. Smoking and Endothelial Dysfunction. Curr. Vasc. Pharmacol. 2020;18:1–11. doi: 10.2174/1573403X14666180913120015</mixed-citation></citation-alternatives></ref></ref-list><fn-group><fn fn-type="conflict"><p>The authors declare that there are no conflicts of interest present.</p></fn></fn-group></back></article>
