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3-(3-[1,2,4]triazolo)-oxatriazolium-5-olate causes vasodilatation by NO-independent activation of soluble guanylate cyclase


Soluble guanylate cyclase (sGC) is a crucial enzyme at NO/cGMP-mediated vasodilation. There are NO-independent mechanisms of sGC activation besides well-known enzyme activation by NO. Since 1966 oxatriazolium-5-olate derivatives are known as hypotensive agents at narcotized animals [1]. But the mechanism of their activity is not clarified. The goal of this research is to examine the ability of 3-(3-[1,2,4]triazolo)-oxatriazolium-5-olate (AS-6) to generate NO, to activate sGC, and to cause vasodilatation.

Material and Methods

The ability of AS-6 to generate NO was estimated by its reaction with oxyhemoglobin in the presence and absence of glutathione. Also NO (nitrite) formation in the presence of AS-6 was measured by the Griess reaction. Activity of sGC was measured by using purified enzyme from porcine lung in the presence of 100 microM AS-6. cGMP formation was measured by immunoenzymatic method. To examine vasodilator activity of AS-6, perfusion pressure responses of isolated tail artery (of male Wistar rats) precontracted with 0.5 mikroM norepinephrine was measured. AS-6 was perfused at concentrations 1·10-9–1·10-5 M.


We demonstrated that AS-6 doesn't generate detectable levels of NO both in the presence and absence of glutathione. AS-6 at concentration 100 microM caused 29 ± 3-fold activation of purified sGC in thiol-independent manner. This activation was 2.0 ± 0.2-fold potentiated by 50 microM allosteric sGC activator YC-1 and completely blocked by heme-dependent sGC inhibitor ODQ. In isolated tail artery AS-6 caused concentration-dependent (1·10-9–1·10-5 M) decrease of perfusion pressure with 26 ± 6 % maximal decrease at 1·10-5 M.


AS-6 causes dose-dependent vasodilatation of isolated systemic artery. It seems to be that AS-6 activates sGC in heme-dependent NO-independent manner.


  1. Kier LB, Al-Shamma A, Campbell D, Patil PN, Tye A: A new class of hypotensive agents. Nature. 1966, 210: 742-

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Correspondence to Anton Bonartsev.

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Open Access This article is published under license to BioMed Central Ltd. This is an Open Access article is distributed under the terms of the Creative Commons Attribution License ( ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Bonartsev, A., Postnikov, A., Artemieva, M. et al. 3-(3-[1,2,4]triazolo)-oxatriazolium-5-olate causes vasodilatation by NO-independent activation of soluble guanylate cyclase. BMC Pharmacol 5 (Suppl 1), P6 (2005).

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