[Imidazoline receptors].

An increasing number of studies suggest that the pharmacology and therapeutic potential of a family of imidazoline receptors continues to generate substantial interest of investigators. This review analyzes the functional role of imidazoline receptors, their subpopulation, distribution in the central and peripheral nervous system and action of related ligands. Besides to their brainstem location where I1-receptor sites play a significant role to regulate and modulate blood pressure, they also are found in different parts of brain with the highest densities in the striatum, pallidum, hippocampus, amygdala, substantia nigra, while I3-receptor sites were revealed in pancreas which enhances insulin secretion, I2-receptors are widely distributed in interpeduncular nucleus, arcuate and pineal gland and take a part in monoamine turnover. It is conclusion that imidazoline receptor in near future can become a therapeutic target in the treatment of diabetes, stroke, mood disorders and hyperalgesic condition.

[Comparative characteristic of angiotensin-converting enzyme inhibitor--captopril and the angiotensin II receptor blokers--losartan action on the oxidative metabolism in experimental hyperlipidemia in rabbits].

The aim of present study--comparative characteristic of captopril and of losartan action on the oxidative metabolism in experimental hyperlipidemia. Experiments carried out on rabbits,which were divided into three groups(ten animal in each group) and orally receiving during 45 days: I control group (cholesterol 500mg/kg + methylthiouracil 100mg/kg, II group-captopril 5 mg/kg + cholesterol 500mg/kg + methylthiouracil 100mg/kg, III group-losartan 8mg/kg + cholesterol-500mg/kg + methylthiouracil 100mg/kg. Activity of superoxide dismutase, catalase, level of malonic dialdehyde, osmotic resistance of erythrocytes and resistanse of LDL to oxidation and concentration of nitric oxide in the blood have been evaluated . The administration of captopril and losartan in experimental hyperlipidemia eqivalently increased activity of SOD and catalase, osmotic resistance of erythrocytes and resistanse of LDL to oxidation, whereas decreased content of malonic dialdehyde compared to the control group . Captopril was more effective than losartan in preserving of nitric oxide. We conclude that captopril and losartan inhibited oxidative stress, which are probably associated with the inhibition of angiotensin 11. Captopril and losartan are safely used in patients during cardio-vascular disease with dyslipidemia.

[Oxidative stress during thyrotoxicosis and its correction].

Oligocrine is a preparation of vegetable origin characterized by anti-inflammatory, antioxidant, immunomodulating properties. Our study shows that administration of L-thyroxine injections (irrespective of the duration) results in elevated synthesis of thyroid hormones and intensification of oxidative stress in experimental animals. These changes are evidenced by accumulation of membrane phospholipide peroxidation products - lipid peroxides in the blood. At that we should point that while dependence of FT3 and FT4 levels on the duration of L-thyroxine administration was insignificant in the experimental model of thyrotoxicosis, intensity of lipid peroxidation increased along with prolongation of injections. Blood levels of free nitric oxide were decreased likely due to the transformation of nitric oxide into peroxinitrite. Oligocrine facilitates to the stabilization of thyroid status and restriction of NO hyperproduction, hypermetabolism and oxidative stress in the body.

[Major pathogenic links of atherosclerosis].

The experimental and clinical data concerning pathogenesis of the atherosclerosis are summarized and analyzed in this article. Major concepts that explain initiation and progressive growth of atherosclerosis such as lipid infiltrations, response to disturbing factors, "response on the keeping of particles" and inflammatory processes are discussed. These concepts are considered as base for integral theory of atherosclerosis according which the inflammatory process in atherosclerosis are the result of the universal response reaction of endothelium to the various disturbing risk factors. Chronic inflammation leads to complex cellular and molecular interactions among cells derived from the endothelium, smooth muscle and several blood cell components and causes oxidative stress, proliferation of smooth muscle cells, oxidative modification of LDL, uptake and macrophage foam cell formation, endothelium dysfunction. Major pathogenic links of atherosclerosis, such as inflammation, oxidative stress, oxidative modification of LDL, lipid infiltration, endothelial dysfunction closely interact, forming close vicious circles which leads to metabolic and morphological disturbances, re-modulation of blood vessels, cardiovascular diseases and such complication as cardiac infarction and stroke. Pathogenic peculiarities of atherosclerosis are the theoretic base to the elaboration of therapeutic strategy. Endothelium may be discussed as a new therapeutic target in atherosclerosis. So far as the leukotrienes play an important role in inflammatory processes, it is suggested that the leukotrienes may be as a potential therapeutic target in cardiovascular diseases.

[Pharmacological correction of hyperactivity of renin-angiotensin-aldosterone system].

Reference data on the function of renin-angiotensin-aldosterone system (RAAS) and pharmacological correction of its hyperactivity are summarized and analyzed in the paper. RAAS plays important role in the development and worsening of hypertension, facilitates proliferation of smooth muscle and heart cells. The hyperactivity of RAAS promotes the development of cardiovascular complications, such as myocardial infarction, stroke, increases cardiovascular mortality and morbidity. Pharmacological correction of RAAS hyperactivity decreases hypertension, prevents occlusion of heart and blood vessels, provides anti-ischemic action, vascular and cardiac protection, improves life style, prevents cardiovascular mortality, such as fatal stroke, myocardial infarction and sudden death. b-blocker inhibitors, angiotensin converting enzyme (ACE) inhibitors, angiotensin AT1-receptors blockers are reviewed as first line therapy of essential hypertension and congestive heart failure. ACT inhibitors, AT1- receptor blockers decrease total cholesterol, LDL, but increase HDL, beta-blockers decrease HDL. AT1-blockers are alternative drugs for treatment of cardiovascular diseases in those cases where ACE inhibitors are contraindicated or intolerance exists.

Role of leukotrienes in stress-induced damage to the heart.

Experiments on rabbits with epinephrine-induced damage to the heart showed that progression of necrotic degenerative processes in the myocardium is augmented by increased content of prostaglandin F(2alpha)and predominance of constrictive over vasodilatory effects in the E and F(2alpha)prostaglandin system. Twenty-four hours after injection of epinephrine we observed an increase in blood concentrations of myofibrillar fraction of creatine phosphokinase, serotonin and histamine, and the F(2alpha)/E prostaglandin ratio. The concentration of leukotriene B(4)increased during the urgent adaptation period, which correlated with a decrease in elastic properties of erythrocytes. In vitro passage of erythrocytes through a 2.5-micro capillary sieve sharply decreased, which played an important role in the progression of myocardial and cerebral hypoxia and ischemia. Myocardial necrosis and endothelial dysfunction developed 24 h later aggravate these pathological shifts.

Use of zafirlucast, cysteine-containing leukotriene antagonist, in epinephrine-induced heart injury.

Combination of preventive and repeated (after 12 h) injections of zafirlucast in a daily dose of 40 mg/kg to animals with epinephrine-induced heart injury essentially decreased the content of leukotriene C(4), but did not prevent the increase of leukotriene B(4)content in the blood, though decreased its content in comparison with the level observed 24 h after epinephrine injection by 11%. Two injections of zafirlucast had a favorable impact on serotonin content in the myocardium (this parameter decreased by 19%), promoted a decrease in epinephrine content and normalization of the norepinephrine/epinephrine ratio, did not change prostaglandin content and ratio, and slightly decreased histamine content in the myocardium. The effect of zafirlucast can be explained by a decrease of oxidative stress. Zafirlucast decreased blood content of myofibrillar fraction of creatine phosphokinase (by 22%) and slightly improved elastic characteristics of erythrocytes. These results suggest that zafirlucast can be added to combined therapy of necrotic, stress-induced, hypoxic, and ischemic injuries of the myocardium.