[Influence of antihypertensive and metabolic drugs on fatty acids content of lipids in cardiomyocytes of rats with spontaneous hypertension].

Changes in fatty acid composition of lipids are an important factor in the development of arterial hypertension. Therefore, this is very important to research the role of fatty acid spectrum of the blood and tissues in the development of hypertension. The search for effective metabolic drugs and antihypertensive drugs which would have the additional ability to influence the fatty acid composition of lipids in cells is also important today. We have found that hypertensive rats demonstrate the essential decrease of the amount of saturated fatty acids (sFA) and high content of unsaturated fatty acids (usFA). Application of amlodipine increases the level of sFA compared with animals without treatment and the level of usFA tends to decrease. A similar pattern is observed when using bisoprolol and combination of amlodipine with bisoprolol, although the combination is characterized by more significant changes in FA composition of lipids in cardiomyocytes. Treatment with metabolic drug elgacin leads to full recovery of saturated and unsaturated fatty acids in the cardiomyocytes. During the treatment with combinations of amlodipine with elgacin and bisoprolol with elgacin the level of both types of AF was not significantly different from the elgacin action in monotherapy. This study demonstrates the modification of the FA composition of lipids in cardiomyocytes of the spontaneously hypertensive rats. The investigated drugs exhibit a normalizing influence on the ratio between sFA and usFA in cardiomyocytes of the hypertensive rats.

[The effect of amlodipine, bisoprolol on the myocardial ultrastructure of the hypertensive rats].

Calcium channel blockers and beta1-adrenoblockers are effective antihypertensive agents, but their cell protective properties are not investigated well. Spontaneously hypertensive rats received a 10 mg/kg/day amlodipine dose and 25 mg/kg/day bisoprolol dose via an orogastric tube during three months. We performed examination of the myocardium's fragments under a scanning electron microscope. Morphometric investigation of mitochondrions we performed using special program what is named "ORGANELLE". Amlodipine significantly normalizes the ultrastructure of the myocardium. This antihypertensive drug prevented the signs of over-contractility of myofibrils. Amlodipine causes the fusion mitochondrions which has compensatory character on the background of good safety of mitochondrial ultrastructures. Another feature of amlodipine is a significant increase in the number of capillaries. Bisoprolol significantly reduced over-contractility of the myofibrils, but the signs of dystrophic-destructive processes in myofibrils and mitochondrions of cardiomyocytes remained. Bisoprolol improved the condition of the endothelial cells, but the activation of the functional activity of these cells has not been observed. The combined use of two antihypertensive drugs amlodipine and bisoprolol led to a better recovery of myofibrils than their separate use, whereas the effect on mitochondrions noted similar as in the group of rats received bisoprolol and that effect was worse than during amlodipine's monotherapy. Also we didn't reveal a reason to combine these drugs after analysis of the effect of the drug combination on the conditions of blood microvessels, which number was increased compared with hypertensive rats, but significantly less than when rats received only amlodipine. These essential cell-protective effects of amlodipine and bisoprolol in spontaneously hypertensive rats could be a significant additional factor in the treatment of hypertension complicated with pathological changes in the heart.

[Quantum-pharmacological aspects of cardiovascular drugs studying].

Quantum pharmacology allows to study the mechanisms of action of cardiovascular drugs, to predict pharmacological activity and identify the most pronounced pharmacodynamic efficacy and therapeutic activity of new compounds. Calculation of quantum-pharmacological parameters for molecules of beta-blockers (propranolol, atenolol, metoprolol, carvedilol) in aqueous media, research its hydrophobic interaction with receptors allow to form a theoretical basis for the development of new generations of more effective and safe medicines for hypertension treatment. Increased hydrophobicity leads to poor solubility of carvedilol in water and high--in the lipids. The clinical pharmacology of the drug is shown by such indicators as the therapeutic dose, half-life and degree of metabolism in the liver. Due to enhanced interaction with adrenergic receptor effective dose of carvedilol is an order of magnitude lower than other beta-blockers, even with the relatively low bioavailability. Reduced bioavailability of carvedilol versus atenolol, metoprolol and propranolol is caused by elevated metabolism during the first pass through the liver, which is also due to the hydrophobicity of the drug. High solubility in lipids appears to extend the half-life of carvedilol. QSAR studies make an important contribution to the study of the properties of chemical compounds and their pharmacological activity. Software, used for computation of studied properties, has a significant role. A large number of descriptors allows a qualitative and quantitative assessment of the molecules of chemical compounds and prediction of their influence on cardiovascular system.

[Effectiveness of use of omega-3 polyunsaturated fatty acids at physical loads].

On the basis of results of quantum-chemical researches with the analysis of atomic structure of molecule, it is shown that polyunsaturated omega-3 fatty acids have the expressed antioxidant and membranoprotective properties that with bioantioxidants karotenoids--tocopherols--are similar. At application in the sportsmen of medical drug Epadol on the basis of polyunsaturated omega-3 fatty acids it is shown that it brakes the activity of lipid peroxidation simultaneously, that is represented by reduction of maintenance of malonic dialdehyde as one of his eventual foods, and assists the improvement of antioxidant defence, that it contingently the increase of concentration of recovered glutathione in the membranes of red blood cells. Under the action of this medical drug the prooxidative-antioxidative coefficient for sportsmen goes down from 2.44 to 1.34 that specifies on a presence at Epadol of antioxidant properties. At the same time sorption ability of erithrocytes, characterizing functional properties of their membranes under act of Epadol goes down from 35.04 +/- 2.23% to 25.3 +/- 1.07% that counteracts to aggregating of red blood cells. An expediency of application of Ukrainian medical drug Epadol on the basis of polyunsaturated fatty acids in practice of preparation of sportsmen for normalization of structural and functional status of cell membranes as well as of prophylaxis noncontrolled apoptosis come into question.

[Quantum-chemical basics of pharmacokinetics (literary review and own investigations)].

The work is devoted to the use of quantum-pharmacological approaches in pharmacokinetic investigations. The main objective of the pharmacological researches is to find new, more active and less toxic drugs. To date, such a search is carried out empirically. The current approach can not fully meet the needs of medicine in the new drugs, requires considerable time and financial costs and does not meet modern standards of bioethics. Quantum pharmacology leads to the synthesis of drugs with desired properties is much faster and more efficient. Computer prediction of pharmacokinetic and biopharmaceutical properties of biologically active substances can make 50-70% more effective development of original drugs.

[Role of oxidative stress in pathogenesis of atherosclerosis and ischemic heart disease].

New views concerning the role of oxidative stress in pathogenesis of atherosclerosis and ischaemic heart disease have been summarized in literature review, possible approaches to their pharmacologic correction taking into account metabolic imbalances caused by oxidative stress have been considered here.

[Effect of splenosid on lipid peroxidation process and glutathione antioxidant system in rats exposed to fractionated radiation]. / Vplyv splenozydu na protsesy peroksydnoho okyslennia lipidiv ta stan antyoksydantnoï systemy za fraktsionovanoho oprominennia shchuriv.

The dynamics of lipid peroxidation, antioxidant glutathione system condition in blood and viscerals (brain, heart, liver, spleen) of rats which were fractionally irradiated (10 fractions) in the total dose 1.0 Gy and oxidative homeostasis increase of primary and secondary lipid peroxidation products and glutathione system disturbances were established in the irradiated rats. The administration of splenosid diminished the disturbances of oxidative homeostasis but does not completely normalize the latter. The administration of splenosid during the irradiation course and after its finishing is more effective than only during the irradiation course.

[Correction of radiation injuries caused by low-intensity irradiation using antioxidants]. / Korekshchia promenevykh urazhen', sprychynenykh nyz'kointensyvnym oprominenniam, za dopomohoiu antyoksydantiv.

The appearance of active oxygen form beginning and lipid peroxidation's activation (side by side with DNA injury) play the leading role in the mechanism of radiation injury. It is expedient to use antioxydants as prophylactic and early pathogenetic therapy remedies. The paper includes the survey of data from literature about usage of different classes of antioxidants (enzymes, vitamins, thiols and other) during prolonged low intensive radiation action.

[Contractility and energy metabolism in human myocardium in normal state and in various stages of cardiac insufficiency]. / Skorotlyva aktyvnist i enerhetychnyi obmin v miokardi liudyny v normi i na riznykh stadiiakh rozvytku sertsevoi nedostatnosti.

Contractile function and metabolism of byoptates of human myocardium were investigated in the control group and at early stages of heart failure development. Support of the myocardial contractile function at the early stage of the heart failure is provided by intensive use of macroergic phosphates and their insufficient resynthesis. At the late stages of myocardial failure deterioration of the heart muscle relaxation was observed as a result of disturbances in transport of high-ergic phosphates to the sites of their utilization.