Features of the Effects of Serotonin and Dopamine on Changes in Heart Rate Variability in Non-Linear Rats under Conditions of Acute Stress.

Changes in indicators of heart rate variability after a single injection of serotonin (200 µg/kg) or dopamine (60 µg/kg) were analyzed in male non-linear rats at rest and during acute stress. At rest, administration of serotonin is accompanied by an increase in the role of the vasomotor center in the formation of heart rate variability; administration of dopamine causes a moderate weakening of HF waves. In both cases, no sharp shifts in the sympathetic-parasympathetic relations are seen, but a more variable rhythm is formed under the effect of serotonin. Under conditions of acute stress, the increase in HR after injection of serotonin is half as much as in the control series, a trend towards weakening of the power of VLF- and even LF-waves is observed. After dopamine injection, a sharp increase in HR and strain index and a decrease in the power of waves of all spectral ranges and the centralization index are observed at the beginning of stress, but by the 30th min, tachycardia becomes moderate, the powers of all waves are restored; HF waves dominate in the spectrum, but potentiation of VLF- and LF-waves and growth of the centralization index are not observed in contrast to the control series. In general, serotonin and dopamine exhibit stress-limiting properties and moderate activation of sympathoadrenal influences and the suprasegmental level of regulation under stress conditions, but after dopamine injection we observed increased reactivity at the beginning of stress and less variable HR. Therefore, serotonin has more pronounced stress limiting effects, which can be revealed by heart rate variability analysis.

Peculiarities of Heart Rate Variability Changes in Random-Bred Male Rats during Transition into Anesthetic Sleep under Stimulation of Central Neurotransmitter Systems.

General anesthesia with Nembutal (40 mg/kg) dramatically decreased the power of all waves of HRV spectrum in rats, especially in LF and VLF frequency bands, but the HR and respiration rate were little changed. At this, individual spectral peaks in HF range were observed at the same frequencies (1.3-1.5 Hz), which are characteristic of the wakeful state. Preliminary stimulation of noradrenergic system with maprotiline (10 mg/kg) increased the power of HF waves and elevated the respiratory rate in narcotized rats in comparison with the control values, although it did not shift the spectral peak at 1.5 Hz in frequency axis. Preliminary stimulation of cholinergic system with galantamine (2 mg/kg) somewhat decreased the power of HF waves and respiratory rate in narcotized rats (in comparison with the control values); additionally, it shifted HF peak to 1.1-1.4 Hz. Activation of serotonergic system with 5-hydroxytryptophan (50 mg/kg) and fluoxetine (3 mg/kg) decreased the HR, the power of HF waves, and respiratory rate in narcotized rats. It also shifted the spectral peak of HF waves to 0.9-0.95 Hz. Preliminary stimulation of dopaminergic system with L-DOPA (20 ml/kg) and amantadine (20 ml/kg) increased the power of VLF waves in narcotized rats in comparison with the control values. Numerous peaks appeared in HF (1.1-1.2 Hz) and VLF frequency bands. Generally, preliminary stimulation of serotonergic or dopaminergic systems markedly affects the neural activity under following general anesthesia: first aggravates the effect of anesthesia on vital centers in CNS, whereas second weakens the effect of anesthesia at the suprasegmental level of neural control.

Effects of Blockage of Peripheral Choline, Serotonin, and Dopamine Receptors on Heart Rhythm Variability in Rats under Conditions of Stimulation of Neurotransmitter Systems.

Stimulation of the serotoninergic system (5-hydroxytryptophan, 50 mg/kg; fluoxetine, 3 mg/kg) induced a significant increase in HR and a reduction in the amplitude of all waves of the heart rhythm variability. Stimulation of the dopaminergic system (L-DOPA and amantadine, 20 mg/kg each) resulted in a moderate increase in HR and amplitudes of low-frequency (LF) and very-low-frequency (VLF) waves of the heart rhythm variability. Successive blockade of nicotinic (hexamethonium, 7 mg/kg) and muscarinic cholinergic receptors (atropine, 1 mg/kg) leads to a significant decrease in the variability of cardiointervals (almost to complete levelling) both under control conditions and after stimulation of the neurotransmitter systems. Serotonin receptor blockade (promethazine, 2 mg/kg) did not affect HR, but reduced the amplitude of LF- and VLF-waves. Under conditions of serotoninergic system stimulation, the blockade of serotonin receptors was followed by a significant HR acceleration without changes in heart rhythm variability; blockade of dopamine receptors (sulpiride, 1 mg/kg) induced HR acceleration and increase in the amplitude of LF- and VLF-waves; blockade of dopamine receptors under conditions of dopamine system stimulation was followed by a significant increase in HR and a decrease in the amplitude of all waves of the heart rhythm variability. It can be hypothesized that serotonin- and dopaminergic systems affect the heart rhythm via cardiomyocyte receptors and via modulation of activity of the adrenergic and cholinergic systems. The effects of serotonin- and dopaminergic systems can be considered as synergic in the CNS, and antagonistic at the periphery.

Effect of Atropine on Adrenergic Responsiveness of Erythrocyte and Heart Rhythm Variability in Outbred Rats with Stimulation of the Central Neurotransmitter Systems.

Single injection of muscarinic cholinoceptor blocker atropine (1 mg/kg) to outbred male rats reduced ß-adrenergic responsiveness of erythrocytes (by 2.2 times) and the content of epinephrine granules on erythrocytes (by 1.5 times), significantly increased HR and rigidity of the heart rhythm, and manifold decreased the power of all spectral components of heart rhythm variability. Stimulation of the central neurotransmitter systems increased ß-adrenergic responsiveness of erythrocytes (by 15-26%), decreased the number of epinephrine granules on erythrocytes (by 25-40%), and increased HR and cardiac rhythm intensity. These changes were most pronounced after stimulation of the serotoninergic system. Administration of atropine against the background of activation of central neurotransmitter systems did not decrease ß-adrenergic responsiveness of erythrocytes (this parameter remained at a stably high level and even increased during stimulation of the dopaminergic system), but decreased the number of epinephrine granules on erythrocytes, increased HR, and dramatically decreased the power of all components of heart rhythm variability spectrum. The response to atropine was maximum against the background of noradrenergic system activation and less pronounced during stimulation of the serotoninergic system. Thus, substances that are complementary to cholinergic receptors modulated adrenergic effect on the properties of red blood cells, which, in turn, can modulate the adrenergic influences on the heart rhythm via the humoral channel of regulation. Stimulation of central neurotransmitter systems that potentiates the growth of visceral adrenergic responsiveness weakens the cholinergic modulation of the adrenergic influences, especially with respect to erythrocyte responsiveness. Hence, changes in the neurotransmitter metabolism in the body can lead to coupled modulation of reception and reactivity to adrenergic- and choline-like regulatory factors at the level of erythrocyte membranes, which can be important for regulation of heart rhythm.

Effect of Stimulation of Neurotransmitter Systems on Heart Rate Variability and ß-Adrenergic Responsiveness of Erythrocytes in Outbred Rats.

We studied heart rate variability and ß-adrenergic responsiveness of erythrocytes and changes in these parameters in response to single administration of ß-adrenoblocker propranolol (2 mg/kg) in outbred male rats against the background of activation of the noradrenergic, serotonergic, and dopaminergic neurotransmitter systems achieved by 4-fold injections maprotiline (10 mg/kg), 5-hydroxytryptophan (50 mg/kg) combined with fluoxetine (3 mg/kg), and L-DOPA (20 mg/kg) with amantadine (20 mg/kg), respectively. Stimulation of the noradrenergic system moderately enhanced the heart rhythm rigidity and ß-adrenergic responsiveness of erythrocytes. In addition, it markedly augmented the moderating effect of subsequently administered propranolol on LF and VLF components in the heart rate variability and reversed the effect of propranolol on ß-adrenergic responsiveness of erythrocytes. Stimulation of the serotonergic system dramatically decreased all components in the heart rate variability and pronouncedly enhanced ß-adrenergic responsiveness of erythrocytes. Subsequent injection of propranolol slightly restored all components in the heart rate variability and decreased ß-adrenergic responsiveness of erythrocytes to the control level. Stimulation of the dopaminergic system made the heart rate more rigid due to decrease of all components in the heart rate variability; in addition, it slightly but significantly enhanced ß-adrenergic responsiveness of erythrocytes. Subsequent injection of propranolol produced no significant effects on all components in the heart rate variability and on ß-adrenergic responsiveness of erythrocytes. Stimulation of noradrenergic, serotonergic, and dopaminergic neurotransmitter systems produced unidirectional and consorted effects on heart rate variability and ß-adrenergic responsiveness of erythrocytes, although the magnitudes of these effects were different. Probably, the changes in the heart rate variability in rats with stimulated neurotransmitter systems results from modification of the cellular sensitivity in peripheral organs to adrenergic influences. However, the differences in the reactions to ß-adrenoblocker attest to specificity of the mechanisms underlying the changes in membrane reception and adrenergic pathways in every experimental model employed in this study.