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3-(3-[1,2,4]triazolo)-oxatriazolium-5-olate causes vasodilatation by NO-independent activation of soluble guanylate cyclaseстатья
Дата последнего поиска статьи во внешних источниках: 28 мая 2015 г.
- Авторы: Anton Bonartsev, Alexander Postnikov, Marina Artemieva, Natalia Medvedeva
- Журнал: BMC Pharmacology
- Том: 5
- Номер: 1
- Год издания: 2005
- Издательство: BioMed Central
- Местоположение издательства: London
- Первая страница: 6
- Последняя страница: 6
- Аннотация: Background Soluble guanylate cyclase (sGC) is a crucial enzyme at NO/cGMP-mediated vasodilation. There are NO-independent mechanisms of sGC activation besides wellknown 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. Results 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. Conclusion 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.
- Добавил в систему: Артемьева Марина Михайловна