vavilovВавиловский журнал генетики и селекцииVavilov Journal of Genetics and Breeding2500-3259Institute of Cytology and Genetics of Siberian Branch of the RAS10.18699/VJ16.216vavilov-877Research ArticleМоделирование патологийModeling of disordersРенин-ангиотензин-альдостероновая система у крыс линии НИСАГ (ISIAH) со стресс-индуцированной артериальной гипертензиейRenin-angiotensin-aldosterone system in ISIAH rats with stressinduced arterial hypertensionДубининаА. Д.DubininaA. D.

Новосибирск, Россия

Novosibirsk, Russia

dubinina_anastas@mail.ruАнтоновЕ. В.AntonovE. V.

Новосибирск, Россия

Novosibirsk, Russia

ФедосееваЛ. А.FedoseevaL. A.

Новосибирск, Россия

Novosibirsk, Russia

ПивовароваЕ. Н.PivovarovaE. N.

Новосибирск, Россия

Novosibirsk, Russia

МаркельА. Л.MarkelA. L.

Новосибирск, Россия

Novosibirsk, Russia

ИвановаЛ. Н.IvanovaL. N.

Новосибирск, Россия

Novosibirsk, Russia

Федеральное государственное бюджетное научное учреждение «Федеральный исследовательский центр Институт цитологии и генетики Сибирского отделения Российской академии наук»РоссияInstitute of Cytology and Genetics SB RAS Novosibirsk State UniversityRussian FederationФедеральное государственное бюджетное научное учреждение «Федеральный исследовательский центр Институт цитологии и генетики Сибирского отделения Российской академии наук» Федеральное государственное автономное образовательное учреждение высшего образования «Новосибирский национальный исследовательский государственный университет»РоссияInstitute of Cytology and Genetics SB RAS Novosibirsk State UniversityRussian Federation201603022017206954958Copyright © Дубинина А.Д., Антонов Е.В., Федосеева Л.А., Пивоварова Е.Н., Маркель А.Л., Иванова Л.Н., 20172017Дубинина А.Д., Антонов Е.В., Федосеева Л.А., Пивоварова Е.Н., Маркель А.Л., Иванова Л.Н.Dubinina A.D., Antonov E.V., Fedoseeva L.A., Pivovarova E.N., Markel A.L., Ivanova L.N.This work is licensed under a Creative Commons Attribution 4.0 License.https://vavilov.elpub.ru/jour/article/view/877

Благодаря широкому спектру возможностей ренин- ангиотензиновой системы (РАС) в регуляции водно-солевого баланса и артериального давления изменение ее активности на системном или локальном (тканевом) уровнях в настоящее время рассматривается как один из наиболее значимых патогенетических факторов развития эссенциальной гипертонии. Цель работы – исследование циркуляторной и тканевой РАС у крыс НИСАГ со стресс- индуцированной артериальной гипертензией. Была измерена концентрация ренина, ангиотензин-превращающего фермента, ангиотензина II и альдостерона в сыворотке крови методом иммуноферментного анализа, а также исследована экспрессия основных генов РАС в почке, надпочечнике и отделах мозга с помощью полимеразной цепной реакции в реальном времени. Обнаружено, что в почке крыс НИСАГ снижена экспрессия мРНК гена ренина Ren по сравнению с нормотензивными крысами WAG, при этом концентрация ренина в сыворотке крови крыс данных линий не отличается. В то же время у крыс этой гипертензивной линии наблюдалось достоверное увеличение концентраций ангиотензина II и альдостерона в сыворотке крови, что может свидетельствовать о наличии «эктопического» очага синтеза ангиотензина II. В надпочечниках крыс НИСАГ экспрессия генов компонентов РАС не изменена. В структурах мозга показано увеличение экспрессии генов компонентов данной системы: Ren – в гипоталамусе, Асе – в стволе мозга, что подтверждает повышение базальной активности центральной РАС у крыс НИСАГ. Тем не менее проведенное исследование позволяет идентифицировать крыс линии НИСАГ как модель низкорениновой формы гипертонической болезни человека.

Because the renin-angiotensin system (RAS) has a wide range of opportunities in the regulation of fluid and electrolyte balance and arterial pressure, it is currently hypothesized that alterations in systemic circulating or local tissue RAS are some of the most important pathogenetic factors in the development of essential hypertension. The aim of the study was to investigate circulating and local tissue RAS activities in ISIAH rats with stress-induced arterial hypertension. We estimated the serum levels of renin, the angiotensin-converting enzyme, angiotensin II and aldosterone by an enzymelinked immunosorbent assay, and mRNA expression of RAS genes in kidney, adrenals and brain tissues was measured by the real-time polymerase chain reaction. The mRNA expression of the renin gene (Ren) in the ISIAH rats was significantly decreased as compared to the normotensive WAG rats, but plasma renin concentrations had no difference. At the same time, the serum levels of angiotensin II and aldosterone in the ISIAH rats were enhanced, which suggests the existence of an ectopic site of angiotensin synthesis. Expression of RAS genes in the adrenals of hypertensive rats was unchanged. By contrast, a significant increase of RAS genes expression was found in the brain tissues. The mRNA of the Ren gene was increased in the hypothalamus, and the mRNA of Ace gene was increased in the brain stem of the ISIAH rats. This may be indicative of a local increase of RAS activity in the brain tissues of ISIAH rats. Nevertheless, the results of the study define ISIAH rat strain as a model of human low-renin hypertension.

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