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 possibleinvolvement of adrenoreceptors (AR) in the development of pathologicheart rhythm with high-amplitude (> 0.5 s) 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 anda high dose of the β-AR agonist isoproterenol was carried out. Injectionof NiCl₂, which blocks T-type voltage-dependentCa²⁺ channels (T-VDCC), causes in 100%of rats the occurrence of PHRBC accompanied by a decrease in therole of neural influences and an increase in the role of neurohumoralfactors in the mechanisms of heart rate regulation. Activation ofβ-AR causes shifts of physiological parameters qualitatively andquantitatively similar to those observed after NiCl₂ poisoningin rats, but PHRBC does not occur. Pharmacological analysis withpremedication of rats with β-AR antagonists (propranolol, atenolol)or α-AR antagonists (phentolamine) followed by NiCl₂ administrationshowed that β-AR blockade with the nonselective adrenolytic propranololprevents the development of PSRBC in half of the rats. In animalswith 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 heartrhythm regulation is revealed. Blockade of α- and β₁-ARdoes not prevent the development of PHRBC during subsequent NiCl₂ administration,which suggests the participation of β₂-ARin the development of arrhythmia. Administration of the selectiveβ₂-AR agonist clenbuterol to rats leads toa decrease in HRV, including neurohumoral regulation and the appearanceof low-amplitude (< 0.1 s) bradycardic complexes (BC) in 22%of rats. The results obtained by us together with the analysis ofthe literature suggest that β-AR plays an important role in thecomplex changes in the balance of regulatory influences in the occurrenceof PHRBCs. Activation of β₁-AR contributesto increased release of catecholamines by adrenal chromaffin cells,increased role of neurohumoral component of heart rhythm regulationand causes activation of β₂-AR. Blockadeof β₂-AR, on the contrary, reduces the releaseof catecholamines and prevents the development of pathological arrhythmia.The second necessary factor leading to the development of arrhythmiaswith high-amplitude BCs is blockade of T-type calcium channels.