Participation of adrenoreceptors in the mechanisms of pathologic cardiac rhythm induced in newborn rats by nickel chloride administration

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.