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

In different periods of postnatal development, the components of the autonomic nervous system, including specific receptors and neurotransmitters involved in the control of cardiovascular functions, are characterized by significant dynamics and variability. Although in 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 development of 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-AR activation with clonidine hydrochloride (10–6 M) against the background of I f blocker ZD7288 application at 10–9 M and 10–5 M. In 1-week-old rat pups, α2-ARs activation evoked bidirectional changes in CF depending on I f blocker concentration, causing its significant increase at 10–9 M and bidirectional dynamics at 10–5 M. In 3-week-old rat pups, α2-AR stimulation reduced CF, while against the background of preliminary I f blockade, the CF dynamics changed to positive. In adult rats, α2-AR activation against the background of I f blockade caused a decrease in CF. The α2-AR agonist evoked 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 background of I f blockade did not alter the HR dynamics in 3-week-old rats and abolished bidirectional HR changes in adult and 1-week-old animals, causing only a decrease in HR in adults and an increase in HR in newborns. The obtained results demonstrate that α2-adrenergic cardiac regulation is modulated by I f, with the degree and direction of the effects depending on the maturity level of cardiac sympathetic innervation.