Nitroxyl Anion Mediates Relaxation in Mesenteric Arteries from Angiotensin II Hypertensive Mice

Title:Nitroxyl Anion Mediates Relaxation in Mesenteric Arteries from Angiotensin II Hypertensive Mice

Volume: 16 Issue: 1

Author(s): Brandi M. Wynne*, Hicham Labazi, Rita C. Tostes and R. Clinton Webb

Affiliation:

• Department of Physiology, Medical College of Georgia at Augusta University, Augusta, GA 30912,United States

Keywords: Hypertension, nitroxyl anion, nitric oxide, resistance vessel, angiotensin II, VSM.

Abstract: Aims: Nitroxyl anion (HNO) has recently become an emerging candidate in vascular regulation. NO- is a potent vasodilator of both conduit and small resistance vessels and mediates relaxation in a soluble guanylate cyclase-dependent manner. Interestingly, HNO activates voltage-dependent K+ (K+ V) channels, whereas Nitric Oxide (NO) activates calcium-activated K+ Ca channels. To date, there are few studies investigating the role of HNO in hypertension, and the possible mechanisms, which may be altered during this condition. We hypothesized that mesenteric arteries from angiotensin II-induced (AngII) hypertensive mice would exhibit an increased dependence upon NO- for relaxation, which may be mediated through K+ V channels.

Methods and Key Results: C57/Bl6 mice, aged 12-14 weeks were implanted with mini-pumps containing angiotensin II (AngII, 3600ng/kg/min) for 14 days. For this study, we proposed to investigate the role of HNO in the resistance vasculature, and so first order mesenteric arteries were isolated and used in functional studies, or were frozen for Western blot analysis. We observed that mesenteric arteries from AngII mice (AngII) exhibited a decrease in HNO-mediated relaxation, which was endotheliumindependent. With HNO scavenging by L-cysteine [3mM], the maximal acetylcholine (ACh)-mediated relaxation response was decreased in sham, whereas mesenteric arteries from AngII exhibited a decrease in sensitivity. Incubation with the K+ V channel inhibitor, 4-aminopyridine [1mM], decreased AChmediated relaxation responses in sham, but almost completely abolished relaxation in AngII.

Conclusion: We reveal that exogenous HNO-mediated relaxation, via Angeli's Salt, is impaired in mesenteric arteries from AngII-treated mice, yet endogenous HNO-mediated relaxation may be more important during hypertension.

Cite this article as:

Wynne M. Brandi *, Labazi Hicham , Tostes C. Rita and Webb Clinton R. , Nitroxyl Anion Mediates Relaxation in Mesenteric Arteries from Angiotensin II Hypertensive Mice, Current Vascular Pharmacology 2018; 16 (1) . https://dx.doi.org/10.2174/1570161115666170725151509