Russian Journal of PhysiologyRussian Journal of PhysiologyРоссийский физиологический журнал им. И.М. Сеченова0869-81392658-655XThe Russian Academy of Sciences65175410.31857/S0869813924090152AIQGPPEXPERIMENTAL ARTICLESЭКСПЕРИМЕНТАЛЬНЫЕ СТАТЬИResearch ArticleParticipation of adrenoreceptors in the mechanisms of pathologic cardiac rhythm induced in newborn rats by nickel chloride administrationУчастие адренорецепторов в механизмах возникновения патологического сердечного ритма, вызванного у новорожденных крысят введением хлорида никеляKuznetsovS. V.КузнецовС. В.
Russian Federation
ksv@iephb.ruKuznetsovaN. N.КузнецоваН. Н.
Russian Federation
ksv@iephb.ruSechenov Institute of Evolutionary Physiology and Biochemistry Russian Academy of SciencesИнститут эволюционной физиологии и биохимии им. И.М. Сеченова РАН1509202411091488150902022025Copyright ©; 2024, Russian Academy of SciencesCopyright ©; 2024, Российская академия наук2024Russian Academy of SciencesРоссийская академия наукhttps://journals.eco-vector.com/0869-8139/article/view/651754

In experiments on 3-day-old rats to identify the possible involvement of adrenoreceptors (AR) in the development of pathologic heart rhythm with high-amplitude (> 0.5 c) bradycardic complexes (PHRBC) occurring in newborn rats after NiCl2 administration, a comparative analysis of changes in heart rate variability (HRV), heart rate, and respiration after injection of nickel chloride and a high dose of the β-AR agonist isoproterenol was carried out. Injection of NiCl2, which blocks T-type voltage-dependent Ca2+ channels (T-VDCC), causes in 100% of rats the occurrence of PHRBC accompanied by a decrease in the role of neural influences and an increase in the role of neurohumoral factors in the mechanisms of heart rate regulation. Activation of β-AR causes shifts of physiological parameters qualitatively and quantitatively similar to those observed after NiCl2 poisoning in rats, but PHRBC does not occur. Pharmacological analysis with premedication of rats with β-AR antagonists (propranolol, atenolol) or α-AR antagonists (phentolamine) followed by NiCl2 administration showed that β-AR blockade with the nonselective adrenolytic propranolol prevents the development of PSRBC in half of the rats. In animals with pathologic arrhythmia occurring after NiCl2 injection, a rapid increase in the load on the sympathoadrenal system is noted, and the initial (background) instability of the mechanisms of heart rhythm regulation is revealed. Blockade of α- and β1-AR does not prevent the development of PHRBC during subsequent NiCl2 administration, which suggests the participation of β2-AR in the development of arrhythmia. Administration of the selective β2-AR agonist clenbuterol to rats leads to a decrease in HRV, including neurohumoral regulation and the appearance of low-amplitude (< 0.1 c) bradycardic complexes (BC) in 22% of rats. The results obtained by us together with the analysis of the literature suggest that β-AR plays an important role in the complex changes in the balance of regulatory influences in the occurrence of PHRBCs. Activation of β1-AR contributes to increased release of catecholamines by adrenal chromaffin cells, increased role of neurohumoral component of heart rhythm regulation and causes activation of β2-AR. Blockade of β2-AR, on the contrary, reduces the release of catecholamines and prevents the development of pathological arrhythmia. The second necessary factor leading to the development of arrhythmias with high-amplitude BCs is blockade of T-type calcium channels.

В экспериментах на 3-дневных крысятах для выявления возможного участия адренорецепторов (АР) в развитии патологического сердечного ритма с высокоамплитудными (> 0.5 c) брадикардическими комплексами (ПСРБК), возникающего у новорожденных крыс после введения NiCl2, проведен сравнительный анализ изменения показателей вариабельности сердечного ритма (ВСР), частоты сердцебиения и дыхания после инъекции NiCl2 и высокой дозы агониста β-АР изопротеренола. Введение NiCl2, блокирующего кальциевые каналы Т-типа (T-type voltage-dependent Ca2+ channel, T-VDCC), вызывает у 100% крысят возникновение ПСРБК, сопровождающегося снижением роли нервных влияний и возрастанием роли нейрогуморальных факторов в механизмах регуляции сердечного ритма. Активация β-АР вызывает сдвиги физиологических показателей, качественно и количественно сходные с наблюдаемыми после отравления крысят NiCl2, но при этом ПСРБК не возникает. Фармакологический анализ с премедикацией крысят антагонистами β-АР (пропранолол, атенолол) или α-АР (фентоламин) с последующим введением NiCl2 показал, что блокада β-АР неселективным адренолитиком пропранололом предотвращает развитие ПСРБК у половины крысят. У животных с возникающей после инъекции NiCl2 патологической аритмией отмечается резкое увеличение нагрузки на симпатоадреналовую систему, а также выявляется первоначальная (фоновая) неустойчивость механизмов регуляции сердечного ритма. Блокада α- и β1-АР не препятствует развитию ПСРБК при последующем введении NiCl2, что позволяет предполагать участие β2-АР в развитии аритмии. Введение крысятам селективного агониста β2-АР кленбутерола приводит к снижению ВСР, включая нейрогуморальное звено регуляции, и появлению у 22% крысят низкоамплитудных (< 0.1 c) брадикардических комплексов (БК). Полученные нами результаты в совокупности с анализом литературы позволяют полагать, что при возникновении ПСРБК в сложной совокупности изменений баланса регулирующих влияний важная роль принадлежит β-АР. Активация β1-АР способствует усилению выброса катехоламинов хромаффинными клетками надпочечников, возрастанию роли нейрогуморального звена регуляции сердечного ритма и вызывает активацию β2-АР. Блокада β2-АР, наоборот, снижает выброс катехоламинов и препятствует развитию патологической аритмии. Вторым необходимым фактором, приводящим к развитию аритмии с высокоамплитудными БК, является блокада кальциевых каналов Т-типа.

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