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Chemiluminescence-based Assays for Detection of Nitric Oxide and its Derivatives from Autoxidation and Nitrosated Compounds
Published on: February 16, 2022
Nitroxyl (HNO) suppresses vascular Nox2 oxidase activity
Alyson A Miller1, Kate F Maxwell, Sophocles Chrissobolis
1Vascular Biology and Immunopharmacology Group, Department of Pharmacology, Monash University, Melbourne, VIC 3800, Australia.
Free Radical Biology & Medicine
|March 6, 2013
Summary
Nitroxyl (HNO), the redox sibling of nitric oxide (NO), effectively reduces reactive oxygen species production and vasoconstriction mediated by Nox2 oxidase in mouse cerebral arteries. This suggests HNO donors may offer therapeutic benefits for vascular dysfunction.
Area of Science:
- Vascular Biology
- Oxidative Stress
- Pharmacology
Background:
- Nox2 oxidase activity contributes to oxidative stress and vascular dysfunction in various diseases.
- Nitric oxide (NO) is known to reduce reactive oxygen species (ROS) production by endothelial Nox2.
- The role of nitroxyl (HNO), NO's redox sibling, in regulating vascular Nox2 activity is not well understood.
Purpose of the Study:
- To investigate whether nitroxyl (HNO) suppresses vascular Nox2 oxidase activity.
- To examine the effects of HNO donors on Nox2-dependent responses to angiotensin II in mouse cerebral arteries.
Main Methods:
- Utilized Angeli's salt and isopropylamine NONOate (IPA/NO) as HNO donors.
- Measured angiotensin II-stimulated superoxide and hydrogen peroxide production in wild-type (WT) and Nox2-deficient (Nox2(-/y)) mouse cerebral arteries.
- Assessed the impact of HNO on angiotensin II-induced vasoconstriction and responses to other constricting agents.
Main Results:
- Both Angeli's salt and IPA/NO significantly reduced angiotensin II-stimulated superoxide and hydrogen peroxide levels in WT mouse cerebral arteries.
- IPA/NO's effect on superoxide was reversible and abolished by an HNO scavenger, but not by NO scavengers or inhibitors of soluble guanylyl cyclase (sGC) or protein kinase G (PKG).
- Angiotensin II-induced vasoconstriction in WT arteries was largely abolished by IPA/NO, while responses to U46619 and high potassium remained unaffected. IPA/NO had no effect in Nox2(-/y) arteries.
Conclusions:
- Nitroxyl (HNO) suppresses vascular Nox2 oxidase activity through a pathway independent of sGC and cGMP.
- HNO donors demonstrate potential as therapeutic agents for mitigating Nox2-dependent vascular dysfunction.
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