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

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 (EC 50 −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 (R max 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 (EC 50 −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