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 controlling the functions of the cardiovascular system, are characterized by significant dynamics and variability. In humans and animals, α₂-adrenergic receptors (α₂-AR) and hyperpolarization-activated current (If) are widespread and participate in the regulation of many functions, but their modulating role at the stages of formation and development of adrenergic regulation of the developing heart has not been sufficiently studied. The study was conducted on isolated hearts of 1-, 3-week-old and adult sexually mature white rats. The heart rate and coronary flow (CF) of a Langendorff isolated rat heart were studied upon activation of α₂-AR clonidine hydrochloride (10^-6 M) against the background of If block ZD7288 (10^-9 M, 10^-5 M). In the group of newborn rat pups, α₂-AR activation causes a multidirectional change in CF, and against the background of If blockade (10^-9 M) causes a significant increase in CF, and against the background of If blockade (10^-5 M), a multidirectional change in CF is observed. In the group of 3-week-old rat pups, α₂-AR stimulation reduces CF, and against the background of preliminary If blockade, CF dynamics changes to positive. In adult rats, activation of α₂-AR against the background of If blockade causes a decrease in CF. The α₂-AR agonist causes a multidirectional change in heart rate in groups of newborn and adult rats, only in 3-week-old rats there is a decrease in heart rate. Stimulation of α₂-AR against the background of If blockade does not change the dynamics of heart rate in the group of 3-week-old rats, and cancels only multidirectional changes in adult and newborn rat's heart rate, causing a decrease in heart rate, and an increase in heart rate in newborn rats. The obtained results show that α₂-adrenergic regulation of the heart is modulated by If, the degree and direction of effects depends on the level of formation of sympathetic innervation of the heart.

alpha₂-adrenergic receptor, hyperpolarization-activated current, isolated heart, ontogenesis, rat