Nitrogen Oxide, Endothelin-1, and Serotonin in the Blood of Immature Spontaneously Hypertensive Rats.

Endothelial function is an early and sensitive marker of subclinical increase of BP in children and adolescents. It is associated with an imbalance of the key vasoactive factors (NO, endothelin-1, and serotonin). Immature spontaneously hypertensive rats (SHR line) are characterized by increased plasma concentrations of NO and endothelin-1 (by 14.7% and 2.9 times, respectively) and increased serotonin content in the plasma and platelets (by 2.7 and 2.3 times, respectively) in comparison with Wistar-Kyoto rats. Platelet count in the blood of SHR rats is by 50% higher than in Wistar-Kyoto rats.

[Ratio of transcription factor PHF10 splice variants in lymphocytes as a molecular marker of Parkinson's disease].

Parkinson's disease (PD) is the second most common neurodegenerative disorder and causes degeneration of dopaminergic neurons in the nigrostriatal system of the brain. PHF10 is one of the most important regulatory subunits of the SWI/SNF chromatin-remodeling protein complex, which controls the gene function and chromatin state in neurons. Two alternative RHF10 isoforms, PHF10-P and PHF10-S, replace each other in the complex to change the target gene pattern. Expression of the PHF10-P and PHF10-S transcripts in the nigrostriatal system and their ratio in blood lymphocytes were found to change in a mouse model of early clinical stage of PD as compared with control mice. Changes in PHF10-S level were also observed in peripheral blood lymphocytes from patients with early clinical stage of PD. A ratio of the PHF10-P and PHF10-S transcripts in peripheral blood cells was assumed to provide a potential marker of early stage PD.

[THE EFFECT OF SEROTONIN ON THE INOTROPIC FUNCTION OF MYOCARDIUM OF THE LEFT VENTRICLE OF IMMATURE SPONTANEOUSLY HYPERTENSIVE RATS].

The mechanisms of the serotonin effect on the inotropic function of the myocardium of the left ventricle of immature spontaneously hypertensive rats (SHR) are unexplored. It was found that systolic arterial blood pressure of 5-6 weeks SHR rats is 147.5 mm Hg, which is statistically significantly higher (more than 25 mm Hg) than in the same age of normotensive control Wistar- Kyoto rats. The weight of the heart, of the left ventricle myocardium, of the ventricular septum, of the aorta and the force of contraction of the left ventricle of 5-6-week-old SHR rats are increased significantly compared with the control. 0.1 pM serotonin increases and 1.0 pM and 10.0 AM serotonin reduce the force of contraction of the left ventricular myocardium in hypertensive rats, but there is a dose-dependent increase of the force of contraction in the control. Serotonin reduces the time of contraction of the myocardium of the left ventricular of SHR rats, these reactions are less pronounced as compared to the control.

[The influence of selective serotonin re-uptake inhibitor fluoxetine on inotropic function of myocardium in the ontogenesis of rats].

Mechanisms of action of selective serotonin (5-HT) re-uptake inhibitors (SSRIs) on cardiac function in the ontogenetic aspect are not adequately explored. Object--Wistar rats: mature rats, pregnant females and their offspring at the age of 14 days. The positive inotropic reaction was detected to SSRIs fluoxetine (Flu) (0.1, 1.0, 10.0 µM) of the ventricles of adult rats, trittiko (SSRIs) exposed 14-day-old rats during the embryonic period. This is showed that contraction force was increased, the overall time contraction was decreased heavily due to more rapid relaxation. The effect on Flu is saved on the background of 5-HT (1.0 µM). The positive inotropic effect of 5-HT was decreased after the addition of all concentration of Flu. However, a dose-dependent increase of ventricle contraction force was revealed on Flu in mature rats. The positive inotropic effect of Flu, Flu on the back of trittiko in the left ventricle is higher than in the right; on the back of 5-HT is more pronounced in the right ventricle than in the left. The positive inotropic effect is decreased in the ventricles of 14-day-old when the concentration of Flu is increased.

Influence of 5-HT(2) receptor agonist on cardiac pumping function of trained offspring of trained rats.

We studied cardiac pumping function in the offspring of rats subjected to swimming exercise and the offspring of untrained rats. The rat pups were adapted for swimming with stepwise increasing load from day 21 to 70 life. At the age of 21 and 70 days, offspring of trained rats showed lower HR and significantly higher stroke volume and cardiac output than offspring of untrained rats. Agonist of 5-HT(2)-receptors α-methyl-5-hydroxytryptamine maleate (30 µg/kg) reduced enhanced stroke volume in trained offspring born by trained mothers. In trained offspring of untrained rats, the agonist had more pronounced effect on HR.

Increased concentrations of serotonin and 5-hydroxyindoleacetic acid in blood plasma from patients with pulmonary hypertension due to mitral valve disease.

Serotonin content in the plasma and platelets and 5-hydroxyindoleacetic acid concentration in the plasma were shown to increase in patients with pulmonary arterial hypertension due to mitral valve disease. A positive correlation was found between the severity of pulmonary arterial hypertension and concentrations of serotonin (r=0.48) and 5-hydroxyindoleacetic acid in the plasma (r=0.9).

Electron paramagnetic resonance study of nitric oxide production during 5-HT2 receptor blockade in the blood, heart, and liver of rats with myocardial infarction.

The effect of serotonin 5-HT2 receptor blockade on nitric oxide production in rats with myocardial infarction was evaluated by the method of electron paramagnetic resonance. The spectra were recorded in samples of the heart tissue (left and right chambers), liver, and blood. 5-HT2 receptor blockade during myocardial infarction was followed by a decrease in the total content of nitrosyl complexes in the spin trap and R and T conformers of Hb-NO. The percent of T conformers increased in the remaining complexes of Hb-NO. These changes were observed in the heart and, particularly, in the blood. The amount of spin-trap complexes was lower in the liver. Hence, nitric oxide molecules were primarily associated with the spin trap in liver tissue. The decrease in the number of Hb-NO complexes in the blood probably reflects the decrease in the severity of hypoxia due to myocardial infarction. A correlation was found between these changes and physiological state of rats. 5-HT2 receptor antagonist improved general state of rats with infarction and increased survival rate.

[Pharmacological sympatectomy changes heart's inotropic reaction on serotonin in postnatal ontogenesis of rats].

In the present study, the influence of 0.1 microM, 1.0 microM, 10.0 microM serotonin (5-HT) on inotropic function (contraction force, time to peak force, time to relaxation) of desympathetized rats by guanethidine in postnatal ontogenesis was investigated. 5-HT has a positive inotropic effect on atria (178 %) and ventricles (122%) in 21-day old rats. In 21-day old desympathetized rats, serotonin influence on the atrium was depressed by 49 %, while ventricle contraction did not change. Atria contraction force in 100-day old rats increased by 38 %, while ventricle contraction force was decreased by 5-HT. In the 100-day old desympathetized rats, a significant elevation ofinotropic effect of 5-HT in atria by 91% and ventricles by 51% was revealed. It was shown that injection of guanethidine during three weeks since birth changes reaction on 5-HT in postnatal ontogenesis ofrats. In 21-day old desympathetized rats, 5-HT had a negative inotropic effect in the early period after pharmacological sympatectomy, while in the period of compensation the elevation of the positive inotropic effect of 5-HT occurred. Positive inotropic effect of atria in 100-day old desympathetized rats was twice as high as in control group. Our data suggest that there exists an interaction between adrenergic and 5-HT regulation in postnatal ontogenesis of rats.

Adrenergic and serotoninergic regulation of myocardial contractility in patients with various morphofunctional changes in the heart resulting from chronic heart failure.

A relationship between morphofunctional changes in the heart and predominance of adrenergic or serotoninergic influences on the strength of myocardial contraction in the right atrium was revealed in patients with chronic heart failure. During left ventricular hypertrophy, the strength of myocardial contraction in response to serotonin exceeded that induced by epinephrine and was realized via 5-HT2 receptors.

[Changes in blood plasma volume in rats during ontogenesis].

The dynamics of blood plasma volume were studied for the first time in rats during ontogenesis. The significance of blood plasma volume is estimated in the transport of physiologically active substances to cells and target organs during development. The blood plasma volume was measured in male and female rats during embryogenesis on day 18 (E18), perinatal development on E21 and day of postnatal development (P3), and postnatal development on P15 and P30. Body mass was determined in the same animals and correlation was estimated between the blood plasma volume and body mass. The plasma volume increased 1.9-fold from E18 to E21, 1.4-fold from E21 to P3, 2.1-fold from P3 to P15, and 3.4-fold from P15 to P30. The body mass increased 5-fold from E18 to E21, 2-fold from E21 to P3, 2.3-fold from P3 to P15, and 3.2-fold from P15 to P30. The ratio of blood plasma to body mass was the highest on E18 (19%) and decreased twice by E21. This index varied from 5.4 to 4.8% during postnatal development. No sex-related differences in these indices were found in rats. The results obtained make it possible to determine the total content of physiologically active substances on the basis of their plasma concentration and, thereby, estimate the efficiency of secretory organs.

Myocardial contractility after in vitro treatment with class III antiarrhythmic drug Nibentan.

Myocardial contractility was studied in vitro in response to treatment with class III antiarrhythmic drug Nibentan. The contractile response to Nibentan in increasing concentrations of 1.66, 2.5, and 3.5 mM was estimated on strips of animal myocardium and human right atrial auricle.

Functional activity of 5-HT4 receptors in children with congenital heart disease.

The effect of 5-methoxytryptamine (5-HT(4) receptor agonist) on the inotropic function of atrial myocardium was studied in children aged 2 months to 17 years, operated on for congenital heart disease. Functional activity of 5-HT(4) receptors was 8.4 times higher in dysfunction of the atrial septum in comparison with other congenital heart diseases. The positive inotropic effects of 5-HT(4) receptor agonist can promote compensation of myocardial work in children with pathological circulation.

Blockade of beta-adrenoceptors and muscarinic cholinergic receptors modulates effect on nitric oxide on heart rate in rats.

Nitroglycerine in doses of 0.4-1.0 mg/kg decreased the heart rate in rats, which was associated with inhibition of adrenergic influences realized via beta-adrenoceptors. The negative chronotropic effect of sodium nitroprusside in a dose of 1 mg/kg was more significant compared to that of nitroglycerine (by 2-3 times). It was associated with inhibition of adrenergic and stimulation of cholinergic influences mediated via beta-adrenoceptors and muscarinic cholinergic receptors, respectively. During blockade of beta-adrenoceptors and muscarinic cholinergic receptors, sodium nitroprusside increased the time of atrioventricular conduction. These data indicate that function of myocytes in the heart conduction system of rats depends on the PQ interval.

Nitric oxide donors dose-dependently reduce heart rate in rats against the background of blood pressure drop.

The effect of nitroglycerin in increasing doses (0.2-1.0 mg/kg) and sodium nitroprusside (1 mg/kg) on the heart rate, P-Q interval of ECG, and blood pressure was studied on 53 albino rats. NO donors nitroglycerin and sodium nitroprusside directly affected vascular endothelium (the maximum decrease in blood pressure was 28.5 and 57.0%, respectively) and produced a dose-dependent negative chronotropic effect (the maximum decrease in heart rate was 13.6 and 27.0%, respectively). These drugs also affected myocytes of the cardiac conduction system: P-Q interval increased by 16.0-29.7%.

[Effect of sympathectomy on the heart pump function in rats during postnatal ontogenesis]. / Vliianie desimpatizatsii na nasosnuiu funktsiiu serdtsa v postnatal'nom ontogeneze krys.

The influence of guanetidine sympathectomy (30 mg/kg) on the heart pump function in rats during 3 weeks in postnatal ontogenesis has been investigated. Sympathectomy restrains age-dependent establishment of stroke volume, cardiac output and heart rate. The adaptation effects of regular physical training do not develop in the animals with sympathectomy, i.e. heart rate does not decrease and stroke volume does not increase. The initial stage of adaptation of the sympathectomized animals to physical training is accompanied by decrease in stroke volume and remarkable increase in heart rate which indicates the reduction of contractile activity in the myocardium.

Effect of physical training on sulfamethazine acetylation rate.

We studied the rate of sulfamethazine acetylation in athletes and untrained controls aging 18-22 years. The rate of sulfamethazine acetylation in controls was characterized by a bimodal distribution: rapid and slow acetylators constituted 42 and 58%, respectively. The rate of sulfamethazine biotransformation in athletes was characterized by a trimodal distribution: ultrarapid, rapid, and slow xenobiotic acetylators constituted 48.4, 22.6, and 29%, respectively. The ultrarapid acetylation phenotype was probably associated with N-acetyltransferase induction and reflected adaptation to physical exercises