Peracute Myocardial Infarction: Features of the Influence of α2-Adrenoreceptor Stimulation on the Isolated Heart.

We performed a comparative analysis of the effect of α2-adrenoreceptor stimulation on the performance of Langendorff-isolated heart from rats with experimental myocardial infarction in the acute stage and sham-operated animals (control). In animals with peracute myocardial infarction, different agonist concentrations (clonidine, 10-6 and 10-9 M) produced a multidirectional effect on the left-ventricular developed pressure and speed and time parameters of heart contractility. In control rats, both concentrations of the agonist added to the perfused solution reduced contraction force. Clonidine in a concentration of 10-6 M reduced HR in both groups and in a concentration of 10-9 M, it decreased HR in control rats and caused multidirectional changes in rats with myocardial infarction. The coronary flow decreased in all series of experiments.

Effect of Adrenoreceptor Stimulation on Peptidergic Regulation of Cardiac Activity in Newborn Rats.

We studied the effect of adrenoreceptor stimulation on the frequency of spontaneous activity and amplitude-time parameters of isometric contraction of the atrial myocardial strips from newborn rats, as well as the effect of Y receptor stimulation against the background of adrenoreceptor activation. After addition of Y1,5 receptor agonist [Leu31, Pro34] NPY (10-7 M), a tendency to a decrease in the effect of ß1,2-adrenoreceptor agonist isoproterenol (10-5 M) on the frequency of spontaneous activity and atrial myocardial contractility was observed. The age-related features of the effect of NPY on the frequency of spontaneous activity and contractility of myocardial strips from newborn and adult rats were revealed.

α2C-Adrenergic Receptor Blockade Inhibits Langendorff-Isolated Rat Heart Work.

We studied the effect of selective α2C-adrenergic receptor antagonist JP-1302 in concentrations of 10-9-10-6 M on inotropy, chronotropy, and coronary flow in the Langendorff-isolated rat heart. JP-1302 in all studied concentrations decreased the left-ventricular myocardium force contraction, HR, and coronary flow. The maximum inotropic, chronotropic, and vascular effects were observed when the antagonist was applied to the perfused solution in a concentration of 10-7 M. The least pronounced decrease in the studied parameters was observed at JP-1302 concentrations of 10-8 and 10-9 M. The obtained data indicate the participation of this subtype of α2-adrenergic receptors in the regulation of activity of isolated adult rats heart.

Mechanisms of Modulation of Adrenergic Regulation of Spontaneous Activity Rate and Atrial Myocardial Contractility in Early Postnatal Ontogeny in Rats.

We studied combined effect of the ß1,2-adrenoreceptor agonist isoproterenol and the Y1,5 receptor agonist [Leu31, Pro34]neuropeptide Y on the frequency of spontaneous activity and myocardial contractility in 21- and 100-day-old rats. Isoproterenol increased the frequency of spontaneous activity and reduced the main parameters of isometric contraction of the atrial myocardium. When [Leu31, Pro34]neuropeptide Y was added, the frequency of spontaneous activity and the negative inotropic and the positive chronotropic effects of isoproterenol were reduced in 100-day-old rats. In 21-day-olds rats, a tendency to a decrease in the effect of isoproterenol was observed.

Features of α2-Adrenergic Regulation of Isolated Rat Heart after Hypokinesia.

We studied the effect of the α2-adrenergic receptor agonist clonidine hydrochloride (10-9-10-6 M) on the isolated heart of adult rats after 30-day restriction of motor activity. In hypokinetic rats, in comparison with control animals, clonidine caused a positive inotropic effect; the dynamics of coronary flow was changed after stimulation of α2-adrenergic receptors by clonidine in the minimum and maximum concentrations. Moreover, clonidine in concentrations of 10-8 and 10-7 M reduced coronary flow both in the control group and against the background of hypokinesia. Clonidine (10-8-10-6 M) had a negative chronotropic effect in control and hypokinetic animals, while the dynamics of HR was multidirectional, i.e. either an increase or decrease in the effects was observed depending of the agonist concentration. Overall, the data obtained indicate the participation of α2-adrenergic receptors in adaptive processes after motor activity limitation.

Langendorff-Isolated Rat Heart after Acute Experimental Myocardial Infarction.

A comparative analysis of functioning of Langendorff-isolated heart from intact rats, sham-operated rats, and rats with a model of myocardial infarction one day after ligation of the left coronary artery was carried out. No significant differences in inotropic and chronotropic functions of the heart were found in the groups of intact and sham-operated animals. In the group of rats with the myocardial infarction model, an increase in HR and a decrease in the maximum contraction and relaxation rates and left-ventricular developed pressure were shown in comparison with the groups of intact and sham-operated animals. At the same time, in the group of sham-operated animals, a decrease in coronary flow and temporal parameters of contraction was observed.

Delayed Consequences of Experimental Myocardial Infarction: Functional Responses to Stimulation of α2-Adrenoreceptors in the Isolated Heart.

We carried out a comparative analysis of the performance of the heart isolated from healthy rats and in 54 and 120 days after modeling of myocardium infarction. On day 120, the blood supply and heart contraction force increased, while HR did not change. Stimulation of α2-adrenoreceptors with clonidine hydrochloride (10-9 M) reduced the force and rate of contraction and the blood flow in the isolated heart from healthy rats. Stimulation of α2-adrenoreceptors of the isolated heart on day 54 after modeling of myocardium infarction induced a positive inotropic response, bradycardia, and insignificant changes in the heart blood flow. On day 120, stimulation of α2-adrenoreceptors slightly reduced HR and the force of contraction and induced biphasic changes in the coronary flow of the isolated heart.

Blockade of α2-Adrenergic Receptors Inhibits Functional Parameters of Langendorff-Isolated Rat Heart.

We studied the effect of α2-adrenoreceptor antagonist yohimbine in concentrations of 10-9-10-6 M on the inotropy, chronotropy, and coronary flow of the Langendorff-isolated rat heart. It was found that antagonist of α2-adrenoreceptors yohimbine changes all the studied parameters of the isolated heart. The force of left ventricular myocardial contraction, HR, and coronary flow decreased after application of all concentrations of α2-adrenoreceptor antagonist. The maximum inotropic, chronotropic, and vascular effects were observed when the antagonist was applied to the perfused solution in a concentration of 10-9 M. The minimum decrease in coronary flow and HR was observed when yohimbine was applied in a concentration of 10-8 M; minimum effect on myocardial contractility was revealed at α2-adrenoreceptor blocker concentration of 10-7 M.

The Effect of α2-Adrenoreceptors Blockade on the Isolated Rat Heart during the Formation of Sympathetic Innervation.

We studied the effects of the α2-adrenergic receptor antagonist yohimbine (10-9-10-6 M) on inotropy, chronotropy, and coronary flow in the Langendorff-isolated heart from 3- and 6-week-old rats. Yohimbine affected all the studied functional parameters of the isolated heart. The force of contraction of the left ventricular myocardium, HR, and coronary flow decreased at all studied concentrations of the antagonist. The maximum chronotropic effect was observed in the heart from 6-week-old rats in the presence of 10-6 M yohimbine in the perfused solution and in the heart from 3-week-old rats in the presence of 10-9 M yohimbine. The minimum chronotropic and inotropic effect was recorded in the hearts from 6-week-old animals after application of 10-9 M α2-adrenergic receptor blocker and in the hearts from 3-week-old animals at yohimbine concentration of 10-7 M. The least pronounced decrease in coronary flow in 3- and 6-week-old rats was observed at the minimum concentration of yohimbine.

Effect of Clonidine Hydrochloride on Isolated Newborn Rat Heart.

The concentration dependenies of the chronotropic response and changes in blood supply to the isolated heart of 7-day-old newborn rats induced by application of α2-adrenergic receptor agonist clonidine hydrochloride in concentrations of 10-9-10-6 M were revealed. The minimum concentration of α2-adrenergic receptor agonist caused tachycardia, while higher concentrations led to bradycardia. The maximum effect manifesting in a decrease in coronary flow was recorded at the minimum concentration of the agonist, while the highest concentration had no effect on the coronary flow. When comparing these results with those obtained in control adult rats, we found that the most pronounced differences in the chronotropic effects were observed after addition of the minimum concentration of the α2-adrenergic receptor agonist: bradycardia in adult rats and tachycardia in newborns. The maximum differences in coronary flow parameters were observed after addition of α2-adrenergic receptor agonist in the maximum concentration that induced a two-phase response in adult rats and had no effect on the blood supply in newborns.

Comparative Analysis of Cardiac Effects of α1A-Adrenoreceptor Stimulation In Vivo and Ex Vivo in Newborn Rats.

The study examined the effects of α1A-adrenoceptor stimulation on chronotropic function of Langendorff-perfused isolated heart ex vivo and on cardiac chronotropy in vivo in 7-day-old rats. α1A-Adrenergic receptor agonist A-61603 reduced heart chronotropy only in the whole organism. No chronotropic effects of selective stimulation of α1A-adrenergic receptors on isolated hearts were observed in ex vivo experiments. These findings suggest that α1A-adrenergic receptors are not implicated in HR regulation in newborn rats. Bradycardia induced by activation of these receptors in vivo is most likely associated with reflex influences on the heart and changes in the vascular tone in the whole organism.

Effect of α2-Adrenergic Receptor Stimulation on the Isolated Rat Heart against the Background of If Blockade.

The study examined the effect of α2-adrenoreceptor (α2-AR) activation against the background of preliminary blockage of If on the performance of Langerndorff-isolated rat heart. Stimulation of α2-AR in isolated rat hearts against the background of ZD7288 in concentrations of 10-9 M and 3×10-5 M changed the negative dynamics of myocardial inotropy to positive (by 25 and 38%; p<0.05). Activation of α2-AR produced opposite effects on HR. If blockade abolished tachycardia caused by activation of α2-AR; HR deceleration in response to α2-AR agonist against the background of If blocker in a concentration 10-9 M was 41% (p<0.05). We observed negative dynamics of coronary flow (by 38%; p<0.05) in isolated adult rat hearts after application of α2-AR agonist against the background of If blockade (10-9 M).

Effect of Stimulation of α2-Adrenergic Receptors on Action Potential of Working Cardiomyocytes in Rat Atrium.

The study examined the effect of clonidine hydrochloride (10-9-10-5 М) on electrical activity of working cardiomyocytes in rat right atrium. Stimulation of α2-adrenergic receptor with clonidine changed electrical activity of the heart. All tested concentrations of the agonist lengthened the action potential and decreased the firing rate of cardiomyocytes in a dose-dependent manner. The maximum effects of clonidine were observed at concentration of 10-5 М.

Effect of Neuropeptide Y on Action Potential of Working Right Atrial Cardiomyocytes in Early Postnatal Ontogeny.

The effects of neuropeptide Y (10-9-10-6 M) on electrical activity of right atrial cardiomyocytes of rats aging 7, 21, and 100 days were examined in vitro. Neuropeptide Y affected the amplitude-temporal parameters of the action potential in these cells. It decreased the duration of repolarization phase in 7-day-old rats in concentrations of 10-8 and 10-7 M, in 21-day-old rats at 10-8 and 10-6 M, and in 100-day-old at 10-6 M. The data indicate elevation of total membrane potassium current under the action of neuropeptide Y.

Effect of If Current Blockade on Newborn Rat Heart Isolated According to Langendorff.

The study examined the effects of hyperpolarization-activated funny current (If) on HR and coronary flow in Langendorff-isolated hearts from newborn rats. Blockade of If current with ZD7288 changed the examined cardiac parameters. The blocker in a concentration of 10-9 M decreased HR by 26.8% (p≤0.05). In concentrations 10-8, 10-7, 10-6, and 10-5 M ZD7288 produced minor differently directed effects. In a concentration of 10-5 M, ZD7288 reduced coronary flow in the isolated heart (p≤0.01). In other concentrations, the blocker produced no significant effects on coronary flow.

Effect of Neuropeptide Y on Action Potential Generation in Working Cardiomyocytes of the Right Atrium in Rat Heart.

We studied the effect of neuropeptide Y in concentrations of 10-8-10-6 M on electrical activity of adult rat right atrial cardiomyocytes with preserved spontaneous activity. Neuropeptide Y was found to modulate the amplitude-time parameters of action potential: in concentrations of 10-7 and 10-6 M it reduced the membrane potential, increased the amplitude of action potential and duration of the repolarization phase, and reduced the frequency of action potential generation. In concentration of 10-6 M, neuropeptide Y produced stronger effect on the analyzed parameters, while in concentration of 10-8 M it produced no significant changes.

Effect of α2-Adrenoceptor Stimulation on Functional Parameters of Langendorff-Isolated Rat Heart.

We studied the effect of α2-adrenoreceptor agonist clonidine hydrochloride in concentrations of 10-9-10-6 M on inotropy, chronotropy, and coronary flow in Langendorff-isolated heart of adult rats. It was found that α2-adrenoreceptor agonist changed all studied parameters. Left ventricular myocardium contraction force decreased after application of all tested concentrations, the maximum effect was observed at a concentration of 10-6 M. Stimulation of α2-adrenergic receptors in concentrations of 10-8, 10-7, and 10-6 M produced a two-phase effect (initial increase and a subsequent decrease) on the coronary flow. Clonidine hydrochloride in the maximum concentration (10-6 M) caused a decrease in HR in one group and an increase in the other.

Dysfunction of Neuromuscular Synapses in the Genetic Model of Alzheimer's Disease.

The function of synaptic transmission and presynaptic vesicular cycle in the neuromuscular synapses of the diaphragm was studied in transgenic APP/PS1 mice (Alzheimer's disease model). The decrease in the quantal content of end-plate potential, intense depression of the amplitude of terminal plate potentials under conditions of lasting high frequency stimulation (50 Hz), a drastic prolongation of the synaptic vesicle recycling time in APP/PS1 mice in comparison with wild type mice were detected. Manifest dysfunction of the neuromuscular synapses, caused by disordered neurosecretion and recycling of the synaptic vesicles in the presynaptic nerve endings, was detected in the Alzheimer's disease model on transgenic APP/PS1 mice. The study supplemented the notions on the pathogenesis of Alzheimer's disease as a systemic disease, while the detected phenomena could just partially explain the development of motor disorders in this disease.

Adrenoceptors in Dopaminergic Regulation of Rat Myocardial Contractility in Rats During Ontogeny.

The effects of different dopamine concentrations on contractility of myocardium with blocked α- or ß-adrenoceptors were examined in vitro in 21- and 100-day old rats. In myocardial strips with blocked α-adrenoceptors, dopamine (10-5 M) increased the right atrial contractile force. By contrast, this neurotransmitter (10-9-10-5 M) reduced the contractile force of atrial and ventricular strips with blocked ß-adrenoceptors.