FTOX002 A new vasodilator does not induce tolerance in rat aorta and cava vein.

Abstract

The nitrite anion (NO2-) can be the major source of intravascular and tissue storage of nitric oxide (NO), important modulator of vascular tone and blood pressure control. The compound [RU(BPY)2(PY)NO2](PF6)], (RUBPY), releases NO inside the vascular smooth muscle cell in a tissue dependent manner. Long-term treatment with the patients with the NO donors such as nitroglycerin, leads to the development of tolerance characterized by the rapid loss of vasodilator effects. It is believed that the tolerance is a multifactorial process and it involves increased production of vascular reactive oxygen species (ROS), decreased activity of soluble guanylyl-cyclase (sGC) and increased expression and activity of phosphodiesterases. The tolerance may be due to endothelial dysfunction. Therefore, we have hypothesized that RuBPY would induce tolerance in veins and in intact endothelium rat aorta.