nefrНефрологияNephrology (Saint-Petersburg)1561-62742541-9439Pavlov First Saint-Petersburg State Medical University10.24884/1561-6274-2019-23-4-88-95nefr-1726Research ArticleОРИГИНАЛЬНЫЕ СТАТЬИ. ЭКСПЕРИМЕНТАЛЬНЫЕ ИССЛЕДОВАНИЯORIGINAL ARTICLES. EXPERIMENTAL INVESTIGATIONИзменение реактивности сосудов крыс с экспериментальным уменьшением массы функционирующих нефроновChanges in the reactivity of vessels of rats with an experimental decrease in the mass of functioning nephronsИвановаГ. Т.IvanovaG. T.

Иванова Галина Тажимовна - кандидат биологических наук, лаборатория физиологии сердечно-сосудистой и лимфатической систем, старший научный сотрудник.

199034, Санкт-Петербург, наб. Макарова, д. 6, Тел.: 8 (812) 328-07-01

Ivanova Galina Tazhimovna – PhD, senior researcher.

199034, Saint-Petersburg, Makarova Emb., 6, Phone: 8 (812) 328-07-01

tazhim@list.ruЛобовГ. И.LobovG. I.

Лобов Геннадий Иванович - докор медицинских наук, профессор, лаборатория физиологии сердечно-сосудистой и лимфатической систем, заведующий лабораторией.

199034, Санкт-Петербург, наб. Макарова, д. 6, Тел.: +7 921 743-06-08

Lobov Gennadii Ivanovich - PhD, DMedSci, head of laboratory.

199934, Saint-Petersburg, Makarova Emb., 6, Ph. +7 921 7430608

LobovGI@infran.ruhttps://orcid.org/0000-0002-7532-2405БересневаО. Н.BeresnevaO. N.

Береснева Ольга Николаевна - кандидат биологических наук, старший научный сотрудник

197022, Санкт-Петербург, ул. Л. Толстого, д. 17, корп. 54, Тел.: (812) 346-39-26

Olga N. Beresneva - PhD, Nephrology Laboratory of Clinical Physiology of the Kidney, senior researcher.

197022, St-Petersburg , L.Tolstoy st., 17, build. 54, Phone (812)346-39-26

beresnevaolga@list.ruПарастаеваМ. М.ParastaevaM. M.

Парастаева Марина Магрезовна - кандидат биологических наук, лаборатория клинической физиологии почек, старший научный сотрудник.

197022, Санкт-Петербург, ул. Л. Толстого, д. 17, корп. 54, Тел.: (812) 346-39-26

Marina M. Parastaeva - PhD, Nephrology Laboratory of Clinical Physiology of the Kidney senior researcher.

197022, St-Petersburg, L.Tolstoy st., 17, build. 54, Phone (812)346-39-26

marina_parastaeva@list.ruИнститут физиологии им. И.П. ПавловаРоссияI.P Pavlov Institute of PhysiologyRussian FederationНаучно-исследовательский институт нефрологии, Первый Санкт-Петербургский государственный медицинский университет им. И.П. ПавловаРоссияInstitute of Nephrology, First Pavlov St.-Petersburg State Medical UniversityRussian Federation2019230620192348895Copyright © Иванова Г.Т., Лобов Г.И., Береснева О.Н., Парастаева М.М., 20192019Иванова Г.Т., Лобов Г.И., Береснева О.Н., Парастаева М.М.Ivanova G.T., Lobov G.I., Beresneva O.N., Parastaeva M.M.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://journal.nephrolog.ru/jour/article/view/1726Цель

Цель: оценить изменения эндотелийзависимой регуляции тонуса кровеносных сосудов (аорты и верхней брыжеечной артерии) у крыс через 4 месяца после удаления 5/6 почечной ткани.

Материал и методы

Материал и методы. Модель ХБП создавали резекцией 5/6 массы почечной ткани. В экспериментальную группу вошли животные (n=12), подвергнутые нефрэкто-мии (НЭ). Контрольную группу составили ложнооперированные (ЛО) крысы (n=10). Исследования реактивности сосудов проводили на кольцевых сегментах длиной 2 мм, которые вырезали из аорты и верхней брыжеечной артерии (ВБА). Всего было подготовлено 23 сегмента аорты и 17 сегментов ВБА от крыс после НЭ и 18 сегментов аорты и 15 сегментов ВБА от контрольных животных. Для измерения силы сокращений препаратов использовали датчик FORT-10 (WPI, USA). Оценивали амплитуду ответов сосудов, предварительно сокращенных фенилэфрином (1 *10-5 М ), на ацетилхолин (АХ, 1 *10-6 М), а также реакцию на АХ в условиях предварительного воздействия ТЭА (1 x10-3 М) и L-NAME (1 x10-4 М).

Результаты

Результаты. Через 4 месяца после резекции части почечной ткани у крыс развивались артериальная гипертензия - АД в группе НЭ крыс было выше (165, 0±9,8 мм рт.ст) по сравнению с ЛО (127,2±9,7 мм рт. ст., р<0,001), и ремоделирование миокарда (ИММЛЖ у НЭ крыс составлял 2,72±0,11 мг/г по сравнению с 2,35±0,09 мг/ в ЛО группе, р<0,001). НЭ также приводила к уменьшению дилатация фрагментов аорты и ВБА на АХ по сравнению с ЛО животными. В условиях блокады синтеза NO ингибитором NO- синтазы - L-NAME реакция на АХ также была ниже у крыс с НЭ. Предварительная блокада Ca2+-активируемых К+-каналов большой проводимости введением ТЭА приводила к снижению вазодилатации, вызванной АХ, у НЭ крыс по сравнению с ЛО группой.

Заключение

Заключение. Резекция 5/6 массы ткани почек у крыс вызывает снижение реактивности сосудов на АХ. Дисрегуляция тонуса сосудов связана с нарушением продукции/биодоступности NO, синтезируемого эндотелием и ингибированием механизма эндотелиальной гиперполяризации.

The aim

The aim: to evaluate changes in endothelium-dependent regulation of the tone of blood vessels (aorta and superior mesenteric artery) in rats 4 months after the removal of 5/6 renal tissue.

Material and methods

Material and methods. An experimental CKD model was created by resection of 5/6 mass of renal tissue. The experimental group included animals (n = 12), subjected to nephrectomy (NE). The control group consisted of sham-operated (SO) rats (n = 10). Researches of vascular reactivity were performed on ring segments 2 mm long, which were excised from the aorta and superior mesenteric artery (SMA). A total of 23 segments of the aorta and 17 segments of SMA from rats after NE and 18 segments of the aorta and 15 segments of SMA from control animals were prepared. To measure the strength of contractions of the drugs, a FORT-10 sensor (WPI, USA) was used. The effects of acetylcholine (Ach, 1 x10-6 M) on blood vessels, previously exposed to phenylephrine (1 x10-5 M), and the response of vessels to Ach under conditions of prior exposure to TEA (1 x 10-3 mol / l) and L-NAME (1 x10-4 mol / l) were evaluated.

Results

Results. NE for a period of 4 months led to arterial hypertension - BP in the NE group of rats was higher (165, 0 ± 9.8 mm Hg) compared with SO (127.2 ± 9.7 mm Hg, р<0,001), and to myocardial remodeling (LVMI in NE rat was 2.72 ± 0.11 mg / g compared to 2.35 ± 0.09 mg / in the SO group, р<0,001 ). NE led to a decrease in dilatation of aortic and BWA fragments on the ACh compared with LO animals. Under the conditions of NO blocking, the NO synthase inhibitor — L-NAME — also had a lower response to ACh in rats with NE. The preliminary blockade of the Ca2 + -activated K + channels of high conductivity with the introduction of TEA resulted in a decrease in vasodilation caused by ACh in NE rat compared with the SO group.

Conclusion

Conclusion. Resection of 5/6 of the kidney tissue mass in rats causes a decrease in vascular reactivity on the ACh. Endothelial dysfunction of rats after NE is associated with impairment of both NO-related and hyperpolarization-dependent endothelial cells in pathways of the vascular tone regulation.

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