ИСТИНА

Potassium channels play an important role in the regulation of vascular tone. There are four types of potassium channels in vascular smooth muscle cells: voltage-dependent (Kv), Ca-activated (KCa), ATP-sensitive (KATP) and inward rec-tifier potassium channels (KIR). KIR play an important role in forming of membrane potential in vascular smooth muscle cells. Furthermore, their hyperpolarizing in-fluence increases at moderate elevation of extracellular K+ ([K+]out). Increase of [K+]out in a blood flow can happen during active organ metabolism and be one of the mechanisms of functional hyperemia. Besides, KIRactivation my be induced by endothelial-derived hyperpolarizing factor (EDHF), which can be provided, in par-ticular, by a local elevation of [K+]out between vascular endothelial and smooth muscle cells. Potassium ions are not metabolites and local blood flow regulators in every body organ. In this regard, our aim was to define KIR contribution in vascular tone regulation in two functionally different vascular regions of rat distal hindlimb. We hypothesized that KIR contribution in vascular tone regulation may vary in ar-teries of skeletal muscles, and in skin supplying arteries. In the study we used Wistar rats (males), body weight of rats was 277–440 g. Two arteries of skin region were isolated: saphenous artery (inner diameter 598±9 mcm) and ventral branch of saphenous artery (247±15 mcm). Also, we used arteries of lateral and medial heads of gastrocnemius muscle (309±9 mcm). Two-millimeter artery segments were placed in isometric myograph (wire myograph, DMT A/S). During a preconstriction induced by methoxamine (agonist of α1-adrenoreceptors) we registered relaxation induced by two factors: (1) elevation of [K+]out (from 4,5 mM to 15 mM), (2) increase of acetylcholine from 10-8 to10-5M. In order to identify EDHF acetylcholine-induced relaxation was studied during inhibiting of NO-synthase (L-NNA, 10-4M) and cyclooxygenase (indomethacin, 10-5 М). Contribution of KIR in relaxation mechanisms was defined by KIR-blocker (Ba2+, 3·10-5 M). Saphenous artery demonstrated small relaxation induced by increase of [K+]out (only 20% of initial constriction), its branch did not relax almost at all. Meanwhile, arteries of gastrocnemius muscle produced almost complete relaxation (80–100%) at elevation of [K+]out from 4,5 mM to 15 mM. KIR blockade led to a decrease of gastrocnemius arteries relaxation, especially at high [K+]out concentrations (from 9 mM to 15 mM). Combined inhibition of КIR and Na+/K+-ATPase (ouabain, 10-3 M) completely suppressed relaxation induced by [K+]out increase. Endothelium activation induced 80–90% relaxation of each studied artery. After inhibiting of NO-synthase and cyclooxygenase acetylcholine did not induce dilation in saphenous artery and its branch, meanwhile, arteries of gastrocnemius muscle produced 80-100% relaxation. In a presence of Ba2+ EDHF-induced relaxation was significantly decreased, especially at high [K+]out concentrations (from 9 mM to 15 mM). Combined inhibition of КIR and Na+/K+-ATPase completely suppressed EDHF-induced relaxation. Our results propose that arteries of skeletal muscles are more likely to relax at elevating of [K+]out, than skin supplying arteries. Skeletal muscle supplying arteries relax at general [K+]out increase (like as during active muscle metabolism) and at local [K+]out increase (induced by endothelium activation). In both cases studied reactions decreased while КIR were blocked. All in all, КIR are more important for regulating vascular tone of skeletal muscle arteries, than of skin arteries, as it correlates with the functions of these arteries in the organism. Study was supported by RFBR (grant № 16-04-01395-а).