Activation of Sarcolemmal α2 Adrenoceptors Supports Са2+ Homeostasis and Prevents Ventricular Arrhythmia under Sympathetic Stress

Аверин, А. С.; Nakipova, O. V.; Kosarsky, L. S.; Pimenov, O. Yu.; Galimova, M. H.; Nenov, Miroslav N.; Berejnov, A. V.; Alekseev, Alexey E.

doi:10.1134/s0006350919050014

Cited by 3 publications

(2 citation statements)

References 21 publications

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“…The presence of compounds in the TFT group which interact highly specifically with individual AR subtypes may be of great utility in pharmacological studies, because each of the three subtypes plays an important role in CVS pathologies and their correction. For example, blocking β-ARs is one of the main directions in the therapy of various forms of hypertension and chronic heart failure [ 75 , 76 ]; activation of α1-ARs may be considered as a compensatory pathway in the desensitization of the β-AR pathway [ 77 , 78 , 79 ]; and α2 activation may be considered as a cardioprotective pathway preventing adrenergic overload of the heart [ 80 , 81 ] and, as shown in our publications, blocking the development of arrhythmias and Ca-overload in cardiomyocytes [ 82 , 83 ].…”

Section: Snake Venoms: Composition and Propertiesmentioning

confidence: 99%

Cardiovascular Effects of Snake Toxins: Cardiotoxicity and Cardioprotection

Аверин

Utkin

2021

Acta Naturae

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Snake venoms, as complex mixtures of peptides and proteins, affect various vital systems of the organism. One of the main targets of the toxic components from snake venoms is the cardiovascular system. Venom proteins and peptides can act in different ways, exhibiting either cardiotoxic or cardioprotective effects. The principal classes of these compounds are cobra cardiotoxins, phospholipases A2, and natriuretic, as well as bradykinin-potentiating peptides. There is another group of proteins capable of enhancing angiogenesis, which include, e.g., vascular endothelial growth factors possessing hypotensive and cardioprotective activities. Venom proteins and peptides exhibiting cardiotropic and vasoactive effects are promising candidates for the design of new drugs capable of preventing or constricting the development of pathological processes in cardiovascular diseases, which are currently the leading cause of death worldwide. For example, a bradykinin-potentiating peptide from Bothrops jararaca snake venom was the first snake venom compound used to create the widely used antihypertensive drugs captopril and enalapril. In this paper, we review the current state of research on snake venom components affecting the cardiovascular system and analyse the mechanisms of physiological action of these toxins and the prospects for their medical application.

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Section: Snake Venoms: Composition and Propertiesmentioning

confidence: 99%

Cardiovascular Effects of Snake Toxins: Cardiotoxicity and Cardioprotection

Аверин

Utkin

2021

Acta Naturae

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“…Previously, the catalog of myocellular membrane receptors has been expanded to include α2-adrenoceptors (α2-ARs) that in line with other adrenergic receptors (α1- and β-) control the stress-reactive response of cardiomyocytes [ 1 , 2 ]. We have identified that, in addition to the established α2-AR-mediated feedback suppression of sympathetic and adrenal catecholamine release, α2-ARs in cardiac myocytes improve intracellular Ca 2+ handling and support myocardial contractility [ 2 , 3 ]. The evidence indicates that protective potential of α2-AR in cardiomyocytes can be mobilized not only against the deleterious effects of chronic stimulation by excessive catecholamine but also against angiotensinergic loads to mitigate the development of cardiac dysfunctions [ 1 , 4 ].…”

Section: Introductionmentioning

confidence: 99%

Role of α2-Adrenoceptor Subtypes in Suppression of L-Type Ca2+ Current in Mouse Cardiac Myocytes

Evdokimovskii

Jeon

Park

et al. 2021

IJMS

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Sarcolemmal α2 adrenoceptors (α2-AR), represented by α2A, α2B and α2C isoforms, can safeguard cardiac muscle under sympathoadrenergic surge by governing Ca2+ handling and contractility of cardiomyocytes. Cardiomyocyte-specific targeting of α2-AR would provide cardiac muscle-delimited stress control and enhance the efficacy of cardiac malfunction treatments. However, little is known about the specific contribution of the α2-AR subtypes in modulating cardiomyocyte functions. Herein, we analyzed the expression profile of α2A, α2B and α2C subtypes in mouse ventricle and conducted electrophysiological antagonist assay evaluating the contribution of these isoforms to the suppression of L-type Ca2+ current (ICaL). Patch-clamp electro-pharmacological studies revealed that the α2-agonist-induced suppression of ICaL involves mainly the α2C, to a lesser extent the α2B, and not the α2A isoforms. RT-qPCR evaluation revealed the presence of adra2b and adra2c (α2B and α2C isoform genes, respectively), but was unable to identify the expression of adra2a (α2A isoform gene) in the mouse left ventricle. Immunoblotting confirmed the presence only of the α2B and the α2C proteins in this tissue. The identified α2-AR isoform-linked regulation of ICaL in the mouse ventricle provides an important molecular substrate for the cardioprotective targeting.

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Adrenergic Regulation of the Functioning of the Cardiovascular System under Hypothermic Conditions

Galimova,

Averin

2024

Biofizika

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Regulation of the function of the cardiovascular system under and after hypothermia is one of important and relevant tasks in biomedical research. It is because of both – serious complications of hypothermia and the potential outcome benefits with hypothermia used for medicinal purposes. Adrenergic regulation is central for the normal function of the cardiovascular system. There are three types of adrenergic receptors known as α1, α2 and β, the expression levels of which are different in the myocardium and blood vessels. Activation of each of the adrenergic receptor subtypes can cause differently directed effects, which are significantly modified under the conditions of low temperature. The effectiveness of β-adrenergic stimulation decreases and β-adrenergic stimulation can even act like hypothermia, leading to impairment of myocardial function. The severity of the effects of α1 adrenergic agonists both on myocardial tissue and in blood vessels is also diminished, however, sensitivity to stimulation of α1a receptors in blood vessels may increase. The activation of α1 adrenergic receptors mediates protective effect in the heart. The activation of α2 adrenergic receptors has a fairly wide range of protective effects on the heart. However, there is now increasing evidence of direct inotropic and vascular effects mediated by this type of receptor. There is also some evidence that these effects become more pronounced under hypothermia. This review examines the current state of research on the effects of stimulation of certain types of adrenergic receptors under normal and hypothermic conditions, analyzes the mechanisms of physiological action and prospects for their further research.

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Activation of Sarcolemmal α2 Adrenoceptors Supports Са2+ Homeostasis and Prevents Ventricular Arrhythmia under Sympathetic Stress

Cited by 3 publications

References 21 publications

Cardiovascular Effects of Snake Toxins: Cardiotoxicity and Cardioprotection

Cardiovascular Effects of Snake Toxins: Cardiotoxicity and Cardioprotection

Role of α2-Adrenoceptor Subtypes in Suppression of L-Type Ca2+ Current in Mouse Cardiac Myocytes

Adrenergic Regulation of the Functioning of the Cardiovascular System under Hypothermic Conditions

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