ИСТИНА

Dysfunction of NO-cGMP-dependent mechanism associated with most forms of cardiovascular disease, such as hypertension, coronary artery disease, chronic heart failure, seems to be one of the main reason of endothelial-induced vasorelaxation reduction. This dysfunction leads to drop in production of vasodilators and induces synthesis vasoconstrictors. In view of the aforesaid normalization NO-cGMP vasodilatation represent a great interest for practical medicine. Soluble guanilate cyclase (sGC) is the major effector of NO in vascular smooth muscle cells (SMC) and crusial enzyme of NO-cGMP-mediated vasodilation. Regulation of sGC activity can be realized in several manners. The most frequently used way of altering arterial pressure via sGC consists in application of NO-donators – drugs, which can generate NO. This way leads to rapid short-term formation of large amounts of cGMP in SMC. It is convenient to use NO-donators in some cases when it is necessary to reduce arterial pressure in shot time. But it is impossible to use NO-donators for chronic therapy because of tolerance. Also NO can be involved in pathogenesis of oxidative stress. Thus the perspective research area for physiologists and pharmacologists is discovering long-term activators of sGC. Since 1966 oxatriazolium-5-olate derivates are known as hypotensive agents at narcotized animals (Kier LB et al., 1966). But the mechanism of their activity is not clarified. The goal of this research is to examine the ability of one of oxatriazolium-5-olate derivate AS-6 to generate NO, to activate sGC, and to alter systemic arterial pressure at awake rats.