Annals of the Russian academy of medical sciencesAnnals of the Russian academy of medical sciencesВестник Российской академии медицинских наук0869-60472414-3545"Paediatrician" Publishers LLC5510.15690/vramn.v70i2.1312CARDIOLOGY: CURRENT ISSUESАКТУАЛЬНЫЕ ВОПРОСЫ КАРДИОЛОГИИROLE OF BRADIKYNIN IN THE MECHANISM OF ISCHEMIC PRECONDITIONING OF THE HEART. PROSPECTS OF BRADYKININ APPLICATION IN CARDIOSURGICAL PRAXISРОЛЬ БРАДИКИНИНА В МЕХАНИЗМЕ ИШЕМИЧЕСКОГО ПРЕКОНДИЦИОНИРОВАНИЯ СЕРДЦА. ПЕРСПЕКТИВЫ ПРИМЕНЕНИЯ БРАДИКИНИНА В КАРДИОХИРУРГИЧЕСКОЙ ПРАКТИКЕMaslovL. N.МасловЛ. Н.
Russian Federation

доктор медицинских наук, профессор, руководитель лаборатории экспериментальной кардиологии НИИ кардиологии; доцент кафедры экономики природопользования Национального исследовательского Томского политехнического университетаАдрес: 634012, Томск, ул. Киевская, д. 111А, тел.: +7 (3822) 26-21-74

Maslov@cardio-tomsk.ruNaryzhnayaN. V.НарыжнаяН. В.
Russian Federation

кандидат медицинских наук, старший научный сотрудник лаборатории экспериментальной кардиологии НИИ кардиологииАдрес: 634012, Томск, ул. Киевская, д. 111А, тел.: +7 (3822) 26-21-74

natalynar@yandex.ruPodoksenovYu. K.ПодоксеновЮ. К.
Russian Federation

доктор медицинских наук, руководитель отделения реанимации НИИ кардиологииАдрес: 634012, Томск, ул. Киевская, д. 111А, тел.: +7 (3822) 26-21-74

Maslov@cardio-tomsk.ruGorbunovA. S.ГорбуновА. С.
Russian Federation

кандидат медицинских наук, младший научный сотрудник лаборатории экспериментальной кардиологии НИИ кардиологииАдрес: 634012, Томск, ул. Киевская, д. 111А, тел.: +7 (3822) 26-21-74

barabator@sibmail.comZhangY.ЖангИ.
China

доктор философии, профессор и директор отдела физиологии Хебейского медицинского университетаАдрес: Hebei Medical University, 361 East zhongshan Road, Shijiazhuang 050017, China

zhyhenry@hotmail.comPeiJ.-M.ПейЖ.-М.
China

доктор философии, профессор отдела физиологии Четвертого Военно-медицинского университетаАдрес: Fourth Military Medical University, No 169, West Changle Road, Xi'an 710032, Shaanxi Province, China

Jmpei8@fmmu.edu.cnResearch Institute for Cardiology, Tomsk, Russian Federation National Research Tomsk Polytechnic University, Russian FederationНИИ кардиологии, Томск, Российская Федерация Национальный исследовательский Томский политехнический университет, Российская ФедерацияResearch Institute for Cardiology, Tomsk, Russian FederationНИИ кардиологии, Томск, Российская ФедерацияHebei Medical University, Shijiazhuang, ChinaХебейский медицинский университет, Шиджиажуанг, КитайFourth Military Medical University, Xi'an, Shaanxi Province, ChinaЧетвертый Военно-медицинский университет, Сиань, Провинция Шаанси, Китай08042015702Vestnik Rossiiskoi akademii medetsinskikh nauk / Annals of the Russian academy of medical sciencesВестник Российской академии медицинских наук18819507082015Copyright ©; 2015, "Paediatrician" Publishers LLCCopyright ©; 2015, Издательство "Педиатръ"2015"Paediatrician" Publishers LLCИздательство "Педиатръ"https://vestnikramn.spr-journal.ru/jour/about/submissionshttps://vestnikramn.spr-journal.ru/jour/article/view/55

Bradykinin level is increased in myocardium in response to short-term ischemia/reperfusion that is one of the evidences of its trigger role in ischemic preconditioning (IP). Pharmacological induced increase of endogenous bradykinin and kallidin-like peptide levels in myocardium enhances cardiac tolerance to impact of ischemia / reperfusion. Experiments with genetically modified mice indicate that kinins are involved in preconditioning but they are not the only trigger of IP. The B2-receptor blocking abolishes antiarrhythmic, infarct reducing effects of preconditioning, eliminates IP-induced cardiac tolerance to oxidative stress. Exogenous bradykinin mimics inotropic and cardioprotective effects of IP but does not mimic antiarrhythmic effect of preconditioning. The intracoronary or intravenous bradykinin infusion enhances human heart resistance to ischemia/reperfusion. Implementation of the cardioprotective effect of IP is provided by the activation of multiple signaling pathways that involve: B2-receptor, calcitonin gene-related peptide, NO-synthase, guanylyl cyclase, cGMP, protein kinase G, mitochondrial KATP channels, reactive oxygen species, kinases C, ERK and Akt. To increase of the human heart tolerance to ischemia/reperfusion is necessary to develop B2-receptor agonists devoid hypotensive and pro-inflammatory properties.

Содержание брадикинина в миокарде увеличивается в ответ на кратковременную ишемию–реперфузию, что является одним из доказательств его триггерной роли в ишемическом прекондиционировании (ИП). Фармакологически индуцированное увеличение в миокарде уровня эндогенного брадикинина и каллидин-подобного пептида повышает устойчивость сердца к действию ишемии–реперфузии. Эксперименты на генетически модифицированных мышах свидетельствуют о том, что кинины участвуют в прекондиционировании, но они не являются единственными эндогенными триггерами ИП. Блокада В2рецепторов устраняет антиаритмический, инфаркт-лимитирующий эффекты прекондиционирования, элиминирует ИП-индуцированную устойчивость сердца к окислительному стрессу. Экзогенный брадикинин имитирует инотропный, антиапоптозный и кардиопротекторный эффект ИП, но не имитирует антиаритмический эффект прекондиционирования. Интракоронарная или внутривенная инфузия брадикинина усиливает толерантность сердца человека к ишемиия–реперфузии. Реализация кардиопротекторного эффекта ИП осуществляется за счет активации нескольких сигнальных путей, в которых задействованы В2-рецептор, ген-кальцитониновый пептид, NO-синтаза, гуанилатциклаза, цГМФ, протеинкиназа G, митохондриальные КАТФ-каналы, активные формы кислорода, киназы С, ERK и Akt. Для повышения устойчивости сердца человека к ишемии–реперфузии необходима разработка агонистов В2-рецепторов, лишенных гипотензивных и провоспалительных свойств.

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