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DOI: https://doi.org/10.22263/2312-4156.2016.2.34

Lazuko S.S.
The role of the inducible NO-synthase in the regulation mechanisms of the functional activity of the ВК-channels in the coronary vessels of rats adapted to stress
Educational Establishment «Vitebsk State Order of Peoples’ Friendship Medical University», Vitebsk, Republic of Belarus

Vestnik VGMU. 2016;15(2):34-43.

Abstract.
To investigate the influence of the inducible NO-synthase (iNOS) on the functional activity of potassium ion channels activated by calcium with high conduction (ВКСа-channels) in the smooth muscle cells of the coronary vessels of rats in the process of the formation of adaptation to stress.
Experiments were carried out on 134 female white mongrel rats weighing 200-250 g. Adaptation to stress was reproduced by upright immobilization of rats in the plastic box filled with water (t=23±2°C) up to the level of the neck during 8 days. Coronary vessels’ tone and myocardial contractility were investigated on isolated by Langendorff’s method rats’ hearts perfused at the constant coronary flow (10 ml/min) with the standard composition of Krebs-Henseleight solution. The blockade of iNOS was realized with S-methylisothiourea (S-MT, 10-6 M). Tetraethylammonium (TEA), a blocker of ВКСа-channels, was added to the perfusion solution (1 mM) to evaluate the role of these channels in the regulation of the coronary blood flow and myocardial contractility. The contribution of ВКСа-channels to the regulation of coronary vessels’ tone was assessed by TEA-mediated vasoconstriction effect, i.e. the increment of the coronary perfusion pressure. The concentration of iNOS, endothelial NO-synthase (eNOS) and stable products of NO degradation (NO2-/NO3-) were detected with immuno-enzyme assay and spectrophotometric methods, accordingly.
It has been established that the addition of S-MT to the perfusion solution doesn’t lead to any changes of the coronary vessels’ tone and myocardial contractility both in the control group and in the group of the «adapted to  stress». Animals coronary constrictor effect of TEA in the adapted animals was expressed to the same extend as in the control group. A simultaneous blockade of ВКСа-channels and iNOS results in the increase of coronary perfusion pressure by in the group of adapted animals 30% compared with the control data under the same conditions. A typical for the adaptation elevation of NO2-/NO3- concentration was accompanied by a decrease of iNOS and an increase of eNOS concentration.
Conclusions. The adaptation to stress leads to the functional activation of the ВКСа-channels, which reveals itself only after the blockade of iNOS, thus demonstrating strong dependence of their activity on the iNOS-derived nitric oxide.
Key words: ВКСа-channels, adaptation, inducible NO-synthase.

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