The Role of Adrenoreceptors and Calcium Ions in the Pathogenesis of Endocardium Endothelium Damage of Rats Under Stress Action on the Background of Hypercholesterolemia

Keywords: Endocardium, Stress, Hypercholesterolemia, Adrenoreceptors, Calcium


Abstract. Topicality. Endothelial dysfunction is a key link in the pathogenesis, formation and progression of clinical manifestations of a significant number of cardiovascular system diseases. Some pathogenetic links and structures associated with morphofunctional disorders of cardiac endothelial cells under the stress conditions and its combination with hypercholesterolemia need further examination.

The aim of the study was to investigate the role of adrenoreceptors and calcium ions (by using of adrenoreceptors and Ca2+-channels blockers) in the pathogenesis of endocardium endothelium damage (by the content of free fatty acids in it and the number of exfoliated cells) as a result of emotional and pain stress action and its influence on the background of hypercholesterolemia.

Materials and methods of research. An electro-pulse model was used for stress reproduction. The alimentary hypercholesterolemia was simulated by keeping animals on an atherogenic diet during 2 months. To establish the role of the above-mentioned cellular structures in the mechanisms of endothelial cell damage, the following pharmacological drugs were administered to animals: β-adrenoblocker,
α-adrenoblocker and Ca2+-channel blocker. The endocardium endothelium state was studied by using light microscopy, by analyzing the smears-imprints from macropreparations of ventricles by counting the number of endothelial cells in them. The content of free fatty acids was determined by radiochemical method.

Research results. It has been shown that β-adrenoblocker and Ca2+-channel blocker significantly limit the damage of endocardium endothelium of left ventricle under the action of emotional and pain stress, and to a much lesser extent, the same effect has α-adrenoblocker. The protective effect of mentioned preparations under the action of stressor factor against the background of alimentary hypercholesterolemia significantly decreases.

Conclusions. The obtained data, their analysis and comparison with the results of other experimental and clinical studies allow to make certain conclusions about the pathogenesis of endothelial dysfunction under emotional stress, as well as under conditions of its combination with hypercholesterolemia. In particular, an important link in the development of structural and some biochemical changes of endocardial endothelial cells is the toxic effect of catecholamines, which affect the organism’s functional systems mainly by β-adrenoreceptors (involving Ca2+ ions), to a lesser extent – by α-adrenoreceptors.

Key words: endocardium, stress, hypercholesterolemia, adrenoreceptors, calcium.


Bazyka OYe, Dovhanych NV, Yarynkina OA, Starshova OS, Tkhor NV, Kozhukhov SM. A modern approach to the treatment of patients with arterial hypertension and diabetes mellitus: calcium antagonists. J. of the national academy of medical sciences of Ukraine.2019;25(2):149-155.

Barna OM. Therapeutic workshop: current positions of beta-blockers. Liky Ukrainy. 2018;9(225-6):23-26. Available from:

Batushkin VV. Significance of pharmacological blockade of the sympathetic autonomic nervous system by nebivolol in combination with hydrochlorothiazide in patients with hypertension with concomitant metabolic syndrome. Liky Ukrainy. 2017;3(209):57-62. Available from:

Vakulenko OS, Torhonskyy RS. Manifestations of endothelial dysfunction in conditions of hypercholesterolemia and exercise. Scientific developments of young people at the present stage. Kyiv National University of Technology and Design. 2019;530-1.

Vlasenko OM, Butikova OO. Correlation of pharmacological treatment of patients with arterial hypertension in combination with chronic obstructive pulmonary disease. Int. Med. J. 2021;2:5-9.

Vlаsov TD, Petrischev NN, Lаzovskаya OA. Endothelial dysfunction. Do we understand this term properly? Vestnik anesteziologii i reanimatologii. 2020;17(2):76-84. Available from:

Vozna KhI. Endothelium: functional properties and its dysfunction. Infektsiyni khvoroby. 2015;1:66-71.

Gavreliuk SV. Changes in hemodynamic parameters and abdominal aortic endothelial function in the experiment with prolonged vagotonia. Zaporozhye medical journal 2017;19(1):30-34. Available from:

Gavreliuk SV, Chykina IV. Effect of chronic immobilization stress on the development of endothelial dysfunction in rats. Fiziolog. Zh. 2017; 63(2):56-64. Available from:

Galimova LF, Sadykova DI, Leontyeva IV, Slastnikova ES, Kurmaeva NS. The study of flow-mediated vasodilation of the brachial artery and other markers of endothelial function in children with familial hypercholesterolemia. Russian Bulletin of Perinatology and Pediatrics. 2020;65(5):169-175. Available from:

Lemko OI, Vantiukh NV. Endothelial dysfunction in patients with chronic obstructive pulmonary disease: some aspects of medicamental treatment (a literature review). Zaporozh. Med. J. 2021;23(1):138-145. Available from:

Lopatin ZV, Vasylenko VS, Karpovska IeB. The role of endothelial damaging factors in the pathogenesis of overexertion cardiomyopathy in sports athletes. Pediatrics. 2018;9(6):57-62.

Luchko IM, Huranych TV, Tuchak OI, Petrunyak SO, Nazaruk ІО. 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. Art of Medicine. 2019;4(12):80-83.

Maksymovych NA. Endothelial dysfunction and physical development in children with high normal blood pressure. Oxygen and free radicals. 2018;115-117.

Nikitin YeV, Vereshchahina OI. Oxidative stress as one of the most important factors in acute endothelial damage. Infectious diseases. 2019;2(96):22-28.

Pasichnichenko O, Vynohradova O, Luhyna V, Toloknieiev A, Yanchuk, P, Makarchyk M. Endothelium-dependent contraction of the portal vein on the action of catecholamines. Scientific Bulletin of the Lesia Ukrainka East European National University. Biological sciences. 2016;12:193-199.

Rykov SO, Sharhorodska IV, Yakovets AI. Catecholamine-induced morphofunctional disorders and oxidative stress in the retina of rats. Journal of Physiology. 2020;66(2-3):27-36. Available from:

Chursina TIa, Mikhaliev KO. Endothelial dysfunction - pathogenetic factor in the occurrence and progression of heart failure. Modern aspects of military medicine. 2016;23:213-224.

Andrieiev IV, Makukha YM, Kravchenko AM, Gayova LV. Biochemical markers of endothelial dysfunction, their changes under the influence of treatment with various beta-adrenoblockers in young men with myocardial infarction. Wiadomosci Lekarskie (Warsaw, Poland: 1960). 2021;74(3):625-629. Available from:

Daiber A et all. Targeting vascular (endothelial) dysfunction. British journal of pharmacology. 2017;174(12):1591-1619. Available from:

Engin A. Endothelial dysfunction in obesity. Obesity and Lipotoxicity. 2017;345-379. Available from:

Fuenzalida B et all. Maternal supraphysiological hypercholesterolemia associates with endothelial dysfunction of the placental microvasculature. Scientific reports. 2018;8(1):1-10. Available from:

Ghosh A, Gao L, Thakur A, Siu PM, Lai CW. Role of free fatty acids in endothelial dysfunction. J. of biomedical science. 2017;24(1):1-15. Available from:

Kirichenko LL, Golosova AN, Gatsura SV, Korolev AP, Ovsyannikov KV, Struchkov PV. Comparison of endothelial function in patients with stage I-II arterial hypertension and stable angina, receiving various bradycardic agents and perindopril. Cardiovascular Therapy and Prevention. 2020;8(7):25-30.

Kwaifa IK, Bahari H, Yong YK, Noor SM. Endothelial dysfunction in obesity-induced inflammation: molecular mechanisms and clinical implications. Biomolecules. 2020;10(2):291. Available from:

Luchko IM, Guranych TV, Voronych-Semchenko NM, Shlyahovenko OO, Storozhuk LS. Some structural and chemical changes in endocardial endothelium of rats in emotional and pain stress complicated by hypercholesterolemia. Galician Med. J. 2017;24(2):29-32. Available from:

Makolkin VI, Napalkov DA. Modern therapeutic potential of super-selective β1-adrenoblocker nebivolol. Cardiovascular Therapy and Prevention. 2020;5(8):109-116.

Turgut AB et all. Serum levels of the adipokines, free fatty acids, and oxidative stress markers in obese and non-obese preeclamptic patients. Clinical and experimental obstetrics & gynecology. 2021;42(4):473-479. Available from:

Original Research