iNOS-dependent regulation of K_ATP- and BK_Ca-channels of coronary vessels in the experimental diabetes mellitus

Introduction and purpose. Disorder of coronary vessels' tone regulation is an important pathogenetic mechanism of diabetic macro- and microangiopathies. Evaluation of delicate mechanisms of such disorders will favour development of new approaches which may decrease patients' mortality rate from cardiovascular catastrophes. The aim of the research is to estimate of the role of nitric oxide produced by inducible NO-synthase in the mechanisms of regulation of the K_ATP- and BK_Ca-channels of coronary vascular smooth muscle cells in streptozocin-induced diabetes mellitus in rats. Material and methods. Diabetes mellitus was reproduced in female rats with single injection of streptozocin intraperitoneally (50 mg/kg). Coronary vessels' tone and myocardial contractility were investigated on isolated with Langendorff's method hearts. Activity of iNOS was blocked with S-methylisothiourea (S-MT, 10^-6M); K_ATP- and BK_Ca-channels - with glybenclamid (10 μM) and tetraethylammonia (1mM), respectively. Expression of iNOS and eNOS in the myocardium was detected with immunohistochemical method; concentration of the stable products of NO degradation (NO^2-/NO^3-) was determined spectrophotometrically; concentration of iNOS, eNOS, and IL-1β was detected with enzyme-linked immunosorbent assay; concentration of C-reactive protein was estimated with immunoturbidimetric method. Results. Experimental diabetes mellitus results in a decrease of coronary vessels' tone and myocardial contractility and a poor sensitivity of vascular smooth muscle cells to the blockers of their ion channels glybenclamid and tetraethylammonia. These changes associate with hyperproduction of IL-1β, increased lipoperoxidation in the blood and enhanced both expression and activity of iNOS. Oxidation and/or nitrozilation of sulphhydryl groups of redox-sensors in the molecules of the K_ATP- and BK_Ca-channels of the coronary vascular smooth muscle cells during experimental diabetes mellitus may be one from the number of pathogenetic mechanisms of the channelopathy. Conclusions. The functional activity of the K_ATP- and BK_Ca-channels of the coronary vascular smooth cells is significantly impaired in parallel with activation of iNOS in rats with experimental diabetes mellitus.

стрептозоцин-индуцированный сахарный диабет, тонус сосудов, индуцибельная NO-синтаза, К_АТФ-каналы, ВК_Ca-каналы, streptozocin-induced diabetes mellitus, vessels' tone, inducible NO-synthase, K_ATP-channels, BK_Ca-channels

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