Avoiding adverse cardiovascular outcomes with prompt blood pressure control: An economic analysis based on the valsartan antihypertensive long-term use evaluation (VALUE) trial

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 alter systemic arterial pressure at awake rats. 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 10-200 microM AS-6 with alpha[P]GTP as a substrate. To examine hypotensive activity of AS-6 male Wistar rats (200-300 g weight) were catheterized and mean arterial pressure was measured. AS-6 was administrated at doses 0.012-120 mg/kg to rats of experimental group in two days. Control group were administrated with corresponding DMSO solutions. We demonstrated that AS-6 doesn’t generate detectable levels of NO both in the presence and absence of glutathione. AS-6 activated purified sGC in dose-dependent manner with 22-fold maximal activation. This activation could be potentiated by allosteric sGC activator YC-1 and completely blocked by heme-dependent sGC inhibitor ODQ. In vivo AS-6 caused MAP decrease, 5.4 and 8.4 mm Hg, (p 0.05) at doses 12 and 120 mg/kg, respectively. MAP was significantly decreased from 15 min and was stably reduced for 15 min. Intravenous administration of AS-6 leads to prolonged arterial pressure decrease in awake rats. It seems to be that AS-6 activates sGC in heme-dependent NO-independent manner.