Resistance arteries and aorta from Angiotensin II hypertensive mice do not exhibit decreased relaxation responses to Angeli's Salt, a nitroxyl anion donor

The endothelium is an important regulator of vascular tone, releasing various vasoactive substances, including nitric oxide (NO), a primary vasodilating agent. NO can exist in three different redox states; the uncharged NO, the oxidized state, nitrosonium cation (NO+), and the reduced state, nitroxyl anion (NO−). This reduced form, NO−, has recently become an emerging candidate in vascular smooth muscle regulation. We hypothesized that relaxation to the nitroxyl anion donor, Angeli's Salt (AS) in resistance arteries and aorta will be decreased in vessels from Ang II mice. Ang II (90ng/min) or sham mice were killed and first order mesenteric arteries and aorta were isolated. Concentration-response curves (CRC) to AS were performed in phenylephrine contracted vessels in the presence of L-NAME (10−4M), ODQ (3x10−6) or high K+ (14mM or 30mM). Removal of the endothelium did not decrease the relaxation response to AS. The relaxation responses to AS were similar in Ang II and sham mice. Also, no differences were observed between hypertensive and normotensive vessels with NOS inhibition. However, Ang II vessels exhibited a decreased relaxation with sGC inhibition, and increased relaxation in the presence of high K+ (14mM). These data suggest that Ang II vessels may have increased sGC activity/expression and that K+ channel activation via the nitroxyl anion is increased in Ang II hypertensive mice.