Nitroxyl anion mediates relaxation in mesenteric arteries from angiotensin II hypertensive mice

Brandi M. Wynne, Hicham Labazi, Rita C. Tostes, R Clinton Webb

Research output: Contribution to journalArticle

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 endothelium-independent. 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 ACh-mediated 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.

Original languageEnglish (US)
Pages (from-to)93-101
Number of pages9
JournalCurrent Vascular Pharmacology
Volume16
Issue number1
DOIs
StatePublished - Jan 1 2018

Keywords

  • Angiotensin II
  • Hypertension
  • Nitric oxide
  • Nitroxyl anion
  • Resistance vessel
  • VSM

ASJC Scopus subject areas

  • Pharmacology
  • Cardiology and Cardiovascular Medicine

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