INFLUENCE OF L-ARGININE AND FEATURES OF PHARMACOLOGICAL CORRECTION OF THE RAT’S HEART ENDOTHELIUM STATE IN CONDITIONS OF EMOTIONAL PAIN STRESS COMPLICATED BY HYPERCHOLESTEROLEMIA

Nowadays the main pathoendotelioropic factors are poorly studied: stress and increased of blood free cholesterol, and ability to use with the protective purpose of L-arginine as a main substrate for the synthesis of nitric oxide (NO). The purpose of the work was to study the endothelium of myocardium (by number of flattened cells) with emotionally-painful stress, complicated with hypercholesterolemia, in the conditions of application of L-arginine and a number of other pharmacological means. To reproduce the stress electric pulse model was used. Alimentary hypercholesterolemia was simulated in animals with the atherogenic diet. In addition to L-arginine, the following pharmacologic agents were applied: β-adrenoblocator Propranolol, blocator of Ca 2+ channels Phynoptin and blocator of cycloxygenases Indomethacin. The endothelium state of endocard was studied by using optical microscop, analyzing strokes-Prints from ventricular macropreparations. As the results, the use of L-arginine before stressors in animals, which received regular food, limits damage to endothelial surface by 22,2% was defined. At the same time, its application in conditions of combined action of stress and hypercholesterolemia does not give a significant positive result. Among other studied pharmacological means expressed cytoprotective action on the endothelium of left ventricle endocardium of rats have propranolol and phynoptyn, that in emotionally-painful stress reduce the desqamation of endoteliocytes in accordance with 63,9% and 40,1%. Introduction of indomethacin before the action of stress, on the contrary, accompanied by strengthening (by 33,3%) endothelial cell peeling. At stress, complicated hypercholesterolemia, the previous tendency is retained in the applied medication action, but their pharmacological effect is less expressed. Under the influence of Propranolol and Phynoptyn, endothelium damage of endocard decreases, but to a lesser extent, than in the action of one only stressful factor (respectively by 51,9% and 26,9%). The use of indomethacin in these conditions leads to reinforcement the desqamation of endotheliocytes by 50%. The protective effect of L-arginine (as NO donator) on the endothelium is connected, obviously, with two mechanisms: the reduction of the intracellular concentration of Ca 2 + ions through activation in the endoteliocytes cytoplasmic guanilatcyclase and inhibition of platelet aggregation to the surface of these cells. As a result, their analysis and comparison with the data of other literary sources, make the following conclusions: а) oral use of L-arginine significantly prevents endothelium of endocardium damage in the case of emotionally painful stress and is ineffective in stress, complicated hypercholesterolemia; b) in the pathogenesis of structural and functional changes of endoteliocytes and the development of endothelial dysfunction in the conditions of emotionally-painful stress and its combination with hypercholesterolemia as important component is the toxic action of catecholamines, affecting the functional systems of the body mainly via β-adrenoreceptors and with the participation of Са2+ ions. Prostaglandins, obviously, play a protective role, because the blockade of their synthesis by indomethacine deepens the damage of endothelium; c) hypercholesterolemia of alimentar origin potentiates damaging effects of stress on endothelium endocardium, accompanied by a sharp increase in the number of desqamatory cells, and, on the other hand, limits the protective effects of certain pharmacological drugs.