Nitroxyl anion mediates vasorelaxation in salt‐loaded AngII hypertensive mesenteric arteries

Abstract

The endothelium regulates vascular tone, releasing various vasoactive substances, including nitric oxide (NO), a vasodilating agent. NO exists in 3 redox states; the uncharged NO, the oxidized state, nitrosonium cation (NO+), and the reduced state, nitroxyl anion (NO−). NO−, has recently become an emerging candidate in vascular regulation. We hypothesized that relaxation to the NO− donor, Angeli's Salt (AS) in resistance arteries from salt‐loaded (4%) Ang II mice (SL) will be decreased. First order mesenteric arteries from Ang II (90ng/min) or sham mice were isolated for functional studies. Concentration‐response curves to AS and ACh were performed in Phe contracted vessels in the presence of the NO and NO− scavengers (carboxy‐PTIO, L‐cystiene, resp.) or the voltage‐gated K+channel blocker (4‐AP). Vessels from SL mice exhibited an endothelium‐independent decrease in NO− mediated relaxation vs. sham (EC50−5.47± 0.17, intact and −5.71± 0.21, denuded vs. −6.16± 0.17*). Sham vessels exhibited a decrease in NO dependent relaxation (Rmax 77.8 vs. 97.2%*), in contrast to SL vessels. In addition, in SL vessels incubated with L‐cystiene or 4‐AP, ACh mediated relaxation was attenuated (EC50 −4.97± 0.24 vs. −5.81± 0.18*) or abolished (−3.32± 17.37 vs. −5.81± 0.18**) resp. These data suggest that SL mesenteric arteries have an increased dependence upon NO−, mainly via K+V channels. (*p<0.05, **p<0.001) HL074167 RCW