DOI: https://doi.org/10.22263/2312-4156.2020.3.30
Lazuko S.S.
iNOS-dependent modulation of the coronary vessels tonе in experimental diabetes mellitus developing on the background of preliminary adaptation
Vitebsk State Order of Peoples’ Friendship Medical University, Vitebsk, Republic of Belarus
Vestnik VGMU. 2020;19(3):30-40.
Abstract.
Objectives. To evaluate the contribution of inducible NO synthase (iNOS) to the mechanisms of maintaining coronary vascular tone and myocardial contractile function in rats with experimental diabetes mellitus, developing against the background of periodically reproduced episodes of immobilization.
Material and methods. Coronary vascular tone and myocardial contractile function were studied on preparations of rat hearts isolated by the Langendorff”s method and perfused at constant volumetric coronary flow (6, 8, 10 and 15 ml/min) with a standard Krebs-Henselight solution. The iNOS blockade was carried out by S-methylisothiourea (S-MT, 10-6M). Adaptation was carried out by immobilization of animals in supine position in a plastic box filled with water (t=23±2°C) to the neck level during 8 days. Diabetes mellitus in rats was modelled by means of a single intraperitoneal injection of streptozocin (50 mg/kg) diluted in citrate buffer (pH 4.5).
The concentration of stable degradation products of NO (NO2-/NO3-), superoxide dismutase, catalase, diene conjugates and malondialdehyde in the left ventricular homogenate was determined by spectrophotometric method. The content of inducible and endothelial NO synthases (eNOS), interleukin 1β, C-reactive protein in the blood serum of experimental animals was determined by enzyme immunoassay.
Results. Diabetes mellitus, reproduced in rats after preliminary adaptation to short stressful effects, was not accompanied by changes in coronary perfusion pressure and developed intraventricular pressure. Introduction of S-MT to the perfusion solution led to an increase in coronary perfusion pressure, but did not affect the values of the developed intraventricular pressure and the rate of contraction and relaxation of the myocardium (dP/dt). In the «Adaptation + diabetes mellitus» group, an increase in the concentration of iNOS, lipid peroxidation products, was determined against the background of a decrease in antioxidant activity and an increase in the content of inflammatory markers (IL-1β, C-reactive protein) in experimental animals.
Conclusions. Diabetes mellitus, reproduced against the background of periodic episodes of immobilization, is accompanied by an increase in the formation of inducible NO synthase, which under conditions of eNOS deficiency, most likely has adaptive value and is necessary in order to maintain adequate production of vasoactive NO and to prevent possible vasoconstriction caused by persistent hyperglycemia, active forms of oxygen and developing systemic inflammation.
Key words: inducible NO synthase, diabetes mellitus, adaptation to short stress effects, coronary vascular tone.
Financing: The research was conducted within the frames of task 1.2.49 of State Research Programs (GPNI) of the Republic of Belarus.
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Information about authors:
Lazuko S.S. – Candidate of Biological Sciences, associate professor, head of the Chair of Normal Physiology, Vitebsk State Order of Peoples’ Friendship Medical University.
Correspondence address: Republic of Belarus, 210009, Vitebsk, 27 Frunze ave., Vitebsk State Order of Peoples’ Friendship Medical University, Chair of Normal Physiology. E-mail: Этот адрес электронной почты защищён от спам-ботов. У вас должен быть включен JavaScript для просмотра. – Svetlana S. Lazuko.
