nidНефрология и диализNephrology and Dialysis1680-44222618-9801Российское диализное обществоnid-801Research ArticleОРИГИНАЛЬНЫЕ СТАТЬИORIGINAL ARTICLESМетиларгинины крови и нарушение регуляции биодоступности оксида азота у пациентов гемодиализаBlood methylarginines and disturbed regulation of nitric oxide bioavailability in patients of hemodialysisГилинскийМ. А.GilinskyM. A.m.a.gilinsky@physiol.ruАнохинС. И.AnokhinS. I.noemail@neicon.ruКоролеваС. А.KorolevaS. A.noemail@neicon.ruЛатышеваТ. В.LatyshevaT. V.noemail@neicon.ruПетраковаГ. М.PetrakovaG. M.noemail@neicon.ruСуховершинР. А.SuhovershinR. A.noemail@neicon.ruНИИ физиологии СО РАМНРоссияInstitute of Physiology, Siberian branch of RAS, NovosibirskRussian FederationФГУ «Сибирский окружной медицинский центр Федерального медико-биологического агентства» (ФГУ «СОМЦ ФМБА»), г. НовосибирскРоссияSiberian Regional Medical Center, NovosibirskRussian Federation201217062025142102108Copyright © Гилинский М.А., Анохин С.И., Королева С.А., Латышева Т.В., Петракова Г.М., Суховершин Р.А., 20252025Гилинский М.А., Анохин С.И., Королева С.А., Латышева Т.В., Петракова Г.М., Суховершин Р.А.Gilinsky M.A., Anokhin S.I., Koroleva S.A., Latysheva T.V., Petrakova G.M., Suhovershin R.A.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://journal.nephro.ru/jour/article/view/801

Изучение роли метиларгининов (МА) в регуляции биодоступности оксида азота (NO) показало, что монометиларгинин (ММА) и асимметричный диметиларгинин (АДМА) конкурентно угнетают NO-синтазу (NOS). Симметричный диметиларгинин (СДМА) не активен в отношении NOS, но регулирует трансмембранный транспорт L-аргинина – субстрата NOS. Установлено, что при высокой концентрации МА в крови нарушаются многие, зависимые от NO, функции сосудов. Высокие уровни MA способствуют развитию атеросклероза и гипертонии. При помощи ВЭЖХ с электрохимической и флуориметрической детекцией измерены концентрации MA, серотонина (5ОТ), его метаболита (5ГИУК) и катехоламинов в крови здоровых людей и пациентов гемодиализа. Уровни АДМА, ММА и СДМА пациентов значительно превышали уровни контрольной группы. Гемодиализ снижал эти уровни, но не все до нормальных значений. Уровни 5ОТ бедной тромбоцитами плазмы пациентов в 6 раз, а 5ГИУК почти в 30 раз превышали таковые в контроле. Диализ не влиял на уровни аргинина плазмы и 5ОТ тромбоцитов. Значимые корреляции обнаружены между параметрами моноаминов и метиларгининов у пациентов гемодиализа, но не в контрольной группе. Полученные данные свидетельствуют, что при анализе патологии сосудов у пациентов гемодиализа недостаточно приписывать ее любой отдельно взятой из исследованных систем. Необходимо учитывать возможность их взаимодействия и взаимозамещения. Анализ собственных и литературных данных позволяет также считать, что негативная корреляция аргинина и норадреналина отражает особенности реакции на медикаментозный стресс, характерные для гипертонии.

Studies of the role of methylarginines (MA) in the regulation of nitric oxide (NO) bioavailability showed that monomethylarginine (MMA) and asymmetric dimethylarginine (ADMA) competitively inhibit NO-synthase (NOS). Symmetric dimethylarginine (SDMA) is not active in respect of NOS. It however regulates transmembrane transport of L-arginine – a NOS substrate. High MA concentration in blood MA was shown to depresses many vascular functions which depend on NO. High level of MA contributes to the development of atherosclerosis and hypertension. Blood concentrations of MA, serotonin (5-HT), its metabolite (5-HIAA) and catecholamines were measured using HPLC with electrochemical and fluorometric detectors in healthy individuals and hemodialysis patients. The levels of ADMA, MMA and SDMA were significantly higher in hemodialysis than in control group. Hemodialysis reduced these levels, but not completely restored their normal values. Level of 5-HT in platelet-poor plasma was 6 times higher, and 5-HIAA was almost 30 times higher in hemodialysis patients than in the control group. Dialysis had no effect on plasma arginine and platelet 5-HT. Significant correlations were found between monoamines and methylarginines in hemodialysis patients, but not in the control group. Our data suggest that vascular pathology in hemodialysis patients could not be attributed to any systems studied. One should keep in mind their interaction and mutual substitution. Our and literature data allow one to assume that negative correlation between arginine and norepinephrine reflects the peculiarities of reaction to the medication stress which are characteristic for hypertensive patients. This work was supported by RFBR grant 08-04-00951.

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The authors declare that there are no conflicts of interest present.