microcirculationРегионарное кровообращение и микроциркуляцияRegional blood circulation and microcirculation1682-66552712-9756Academician I.P. Pavlov First St. Petersburg State Medical University10.24884/1682-6655-2021-20-3-61-69microcirculation-975Research ArticleОРИГИНАЛЬНЫЕ СТАТЬИ (ЭКСПЕРИМЕНТАЛЬНЫЕ ИССЛЕДОВАНИЯ)ORIGINAL ARTICLES (EXPERIMENTAL INVESTIGATIONS)Биохимическая оценка системы синтеза оксида азота у пренатально стрессированных крысThe biochemical estimation of the nitric oxide system in prenatally stressed ratsБеляеваЛ. Е.BelyaevaL. E.

Беляева Людмила Евгеньевна – канд. мед. наук, доцент, зав. кафедрой патологической физиологии

Республика Беларусь, г. Витебск, пр. Фрунзе, д. 27

Belyaeva Lyudmila E. – Candidate of Medical Sciences, associate professor, head of the Chair of Pathologic Physiology

27, Frunze pr., Vitebsk, Republic of Belarus

lyudm.belyaeva2013@yandex.byПавлюкевичА. Н.PauliukevichH. N.

Павлюкевич Анна Николаевна – м. м. н., старший преподаватель кафедры патологической физиологии

Республика Беларусь, г. Витебск, пр. Фрунзе, д. 27

Pauliukevich Hanna N. – Master of Medical Sciences, senior lecturer of the Chair of Pathologic Physiology

27, Frunze pr., Vitebsk, Republic of Belarus

anna.fedchenko.89@mail.ruУчреждение образования «Витебский государственный ордена Дружбы народов медицинский университет»БеларусьVitebsk State Order of Peoples’ Friendship Medical UniversityBelarus2021270920212036169Copyright © Беляева Л.Е., Павлюкевич А.Н., 20212021Беляева Л.Е., Павлюкевич А.Н.Belyaeva L.E., Pauliukevich H.N.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.microcirc.ru/jour/article/view/975

Введение. Развитие беременности в неблагоприятных условиях может способствовать нарушению образования оксида азота NO у потомства в постнатальной жизни и «программировать» заболевания сердечно-сосудистой системы потомства. Выяснение особенностей и механизмов нарушения функционирования системы синтеза и действия оксида азота после перенесенного пренатального стресса позволит расширить представления о патогенезе целого ряда заболеваний сердечно-сосудистой системы и предложить новые подходы к их профилактике и лечению. Цель – оценить характер образования и действия оксида азота у половозрелых крыс, матери которых во время беременности подвергались воздействию хронического «непредсказуемого» стресса. Материалы и методы. Из беременных крыс сформировали группы «контроль» и «стресс» (по 20 голов). Крыс группы «стресс» подвергали неоднократным стрессорным воздействиям через различные промежутки времени: лишению пищи в течение суток, иммобилизации в воде комнатной температуры в течение 20 мин, контакту с экскрементами кошек в течение суток. В сыворотке крови 3-месячного потомства (n=96, в том числе группа «контроль» самцы – 24, группа «контроль» самки – 26, группа «стресс» самцы – 22, группа «стресс» самки – 24) определяли содержание конечных продуктов деградации NO – нитратов/нитритов (NO3–/NO2–), концентрацию эндотелиальной (eNOS) и индуцибельной (iNOS) изоформ NO-синтазы, ингибитора NO-синтазной реакции – асимметричного диметиларгинина (АДМА), содержание циклического гуанозинмонофосфата (цГМФ), концентрацию продуктов перекисного окисления липидов (ПОЛ) – диеновых конъюгатов (ДК) и малонового диальдегида (МДА), а также концентрацию C-реактивного белка высокочувствительным методом (hsСРБ). Результаты. Было обнаружено снижение содержания eNOS и цГМФ (на 12,9 и 31,9 % соответственно), повышение концентрации iNOS, hsСРБ и АДМА (на 49,9, 20,3 и 63,1 % соответственно) без статистически значимых изменений уровня NO3–/NO2–, а также увеличение содержания ДК на 21,1 % и МДА в 1,5 раза в сыворотке крови пренатально стрессированных самцов, по сравнению с самцами, родившимися у крыс группы «контроль». У самок, матери которых подвергались хроническому «непредсказуемому» стрессу во время беременности, были обнаружены тенденция к снижению концентрации eNOS, увеличение содержания iNOS на 30,6 %, hsСРБ на 23,9 % и МДА в 2,3 раза (сравнение с соответсвующими показателями группы «контроль» самки) без статистически значимых изменений в концентрации цГМФ, АДМА, NO3–/NO2– и ДК в сыворотке крови. Выводы. Выявленные изменения в системе образования и функционирования оксида азота у пренатально стрессированных крыс-самцов могут свидетельствовать о высоком риске поражения у них сердечно-сосудистой системы.

Introduction. Pregnancy development following unfavorable conditions could facilitate disorders of nitric oxide (NO) production during offspring’s postnatal life and «program» offspring’s cardiovascular diseases. Investigation of particular features and mechanisms of nitric oxide synthesis and action disorders following prenatal stress will promote expansion of considerations about pathogenesis of different cardiovascular diseases and propose new approaches to their prevention and management.The aim of the investigation is to assess the nature of nitric oxide synthesis and action in mature rats whose mothers were exposed to chronic «unpredictable» stress during pregnancy. Materials and methods. Pregnant rats were subdivided into the «control» and «stress» groups (in 20 animals). The rats from the «stress» group were exposed to multiple different stressors at various intervals, such as 1-day famine; 20-min. immobilization in the water at room temperature; 1-day contact with cats’ excrements. In the blood serum of 3-mo offspring (n=96, including «control» males – 24, «control» females – 26, «stress» males – 22, «stress» females – 24) concentration of the stable products of NO degradation – nitrates/nitrites (NO3–/NO2–), endothelial (eNOS) and inducible (iNOS) isoforms of the NO-synthase, inhibitor of NO-synthase asymmetric dimethylargininne (ADMA), cyclic guanosine monophosphate (cGMP), lipid peroxidation products – diene conjugates (DC) and malonic dialdehyde (MDA) and C-reactive protein (hsCRP) was detected. Results. The decrease of eNOS and cGMP concentration (by 12.9 and 31.9 %, respectively), increase of iNOS, hsCRP and ADMA concentration (by 49.9, 20.3 и 63.1 %, respectively) without statistically significant fluctuation in the NO3–/NO2– level and accumulation of DC and MDA by 21.1 % and 1.5 times in a prenatally stressed male rats’ blood serum were found (as compared with «control» male rats). In a blood serum of female rats, whose mothers were exposed to chronic «unpredictable» stress during pregnancy, a tendency to eNOS concentration decreasing, and increase of iNOS by 30.6 %, hsCRP by 23.9 % and MDA by 2.3 times without statistically significant changes in cGMP, ADMA, NO3–/NO2–, and DC concentration were detected (as compared with «control» female rats). Conclusion. Identified changes of the nitric oxide system synthesis and action in the prenatally stressed male rats could argue the high risk of their cardiovascular system lesion.

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