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Abstract <p>In different periods of postnatal development, the componentsof the autonomic nervous system, including specific receptors andneurotransmitters involved in the control of cardiovascular functions, arecharacterized by significant dynamics and variability. Althoughin humans and animals, α<sub>2</sub>-adrenoceptors (α<sub>2</sub>-ARs)and the hyperpolarization-activated current (<i>I</i> <sub>f</sub>)are widespread and involved in the regulation of multiple functions,their modulatory role at different stages of the formation and developmentof cardiac adrenergic regulation has been insufficiently studied.The present study was carried out on isolated hearts of 1-week-old,3-week-old, and adult white rats. Heart rate (HR) and coronary flow(CF) in the Langendorff rat heart were recorded upon α<sub>2</sub>-ARactivation with clonidine hydrochloride (10<sup>–6</sup> M)against the background of <i>I</i> <sub>f</sub> blockerZD7288 application at 10<sup>–9</sup> M and 10<sup>–5</sup> M.In 1-week-old rat pups, α<sub>2</sub>-ARs activationevoked bidirectional changes in CF depending on <i>I</i> <sub>f</sub> blockerconcentration, causing its significant increase at 10<sup>–9</sup> Mand bidirectional dynamics at 10<sup>–5</sup> M. In3-week-old rat pups, α<sub>2</sub>-AR stimulation reducedCF, while against the background of preliminary <i>I</i> <sub>f</sub>&#xa0;blockade,the CF dynamics changed to positive. In adult rats, α<sub>2</sub>-ARactivation against the background of <i>I</i> <sub>f</sub> blockadecaused a decrease in CF. The α<sub>2</sub>-AR agonistevoked bidirectional changes in HR in 1-week-old and adult rats,causing only a significant reduction in HR in 3-week-old rat pups.Stimulation of α<sub>2</sub>-ARs against the backgroundof <i>I</i> <sub>f</sub> blockadedid not alter the HR dynamics in 3-week-old rats and abolished bidirectionalHR changes in adult and 1-week-old animals, causing only a decreasein HR in adults and an increase in HR in newborns. The obtainedresults demonstrate that α<sub>2</sub>-adrenergic cardiac regulationis modulated by <i>I</i> <sub>f</sub>,with the degree and direction of the effects depending on the maturitylevel of cardiac sympathetic innervation.</p>

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Stimulation of Alpha-2 Adrenoreceptors against the Background of Hyperpolarization-Activated Current Blockade at Different Formation Stages of Cardiac Adrenergic Innervation

  • 期刊论文

  • 发表日期：

    2025年10月1日

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  • A. M. Kuptsova,
  • N. I. Ziyatdinova,
  • A. L. Zefirov,
  • N. G. Iskakov,
  • T. L. Zefirov

摘要

Abstract

In different periods of postnatal development, the componentsof the autonomic nervous system, including specific receptors andneurotransmitters involved in the control of cardiovascular functions, arecharacterized by significant dynamics and variability. Althoughin humans and animals, α2-adrenoceptors (α2-ARs)and the hyperpolarization-activated current (I f)are widespread and involved in the regulation of multiple functions,their modulatory role at different stages of the formation and developmentof cardiac adrenergic regulation has been insufficiently studied.The present study was carried out on isolated hearts of 1-week-old,3-week-old, and adult white rats. Heart rate (HR) and coronary flow(CF) in the Langendorff rat heart were recorded upon α2-ARactivation with clonidine hydrochloride (10–6 M)against the background of I f blockerZD7288 application at 10–9 M and 10–5 M.In 1-week-old rat pups, α2-ARs activationevoked bidirectional changes in CF depending on I f blockerconcentration, causing its significant increase at 10–9 Mand bidirectional dynamics at 10–5 M. In3-week-old rat pups, α2-AR stimulation reducedCF, while against the background of preliminary I f blockade,the CF dynamics changed to positive. In adult rats, α2-ARactivation against the background of I f blockadecaused a decrease in CF. The α2-AR agonistevoked bidirectional changes in HR in 1-week-old and adult rats,causing only a significant reduction in HR in 3-week-old rat pups.Stimulation of α2-ARs against the backgroundof I f blockadedid not alter the HR dynamics in 3-week-old rats and abolished bidirectionalHR changes in adult and 1-week-old animals, causing only a decreasein HR in adults and an increase in HR in newborns. The obtainedresults demonstrate that α2-adrenergic cardiac regulationis modulated by I f,with the degree and direction of the effects depending on the maturitylevel of cardiac sympathetic innervation.