ROLE OF BRADIKYNIN IN THE MECHANISM OF ISCHEMIC PRECONDITIONING OF THE HEART. PROSPECTS OF BRADYKININ APPLICATION IN CARDIOSURGICAL PRAXIS

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Abstract

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.

 

About the authors

L. N. Maslov

Research Institute for Cardiology, Tomsk, Russian Federation
National Research Tomsk Polytechnic University, Russian Federation

Author for correspondence.
Email: Maslov@cardio-tomsk.ru

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

Russian Federation

N. V. Naryzhnaya

Research Institute for Cardiology, Tomsk, Russian Federation
National Research Tomsk Polytechnic University, Russian Federation

Email: natalynar@yandex.ru

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

Russian Federation

Yu. K. Podoksenov

Research Institute for Cardiology, Tomsk, Russian Federation

Email: Maslov@cardio-tomsk.ru

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

Russian Federation

A. S. Gorbunov

Research Institute for Cardiology, Tomsk, Russian Federation

Email: barabator@sibmail.com

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

Russian Federation

Y. Zhang

Hebei Medical University, Shijiazhuang, China

Email: zhyhenry@hotmail.com

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

China

J.-M. Pei

Fourth Military Medical University, Xi'an, Shaanxi Province, China

Email: Jmpei8@fmmu.edu.cn

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

China

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