Nitroxyl, the novel redox sibling of NO, suppresses cerebrovascular NADPH oxidase

Kemp-Harper, B., Ravi, R., Bullen, M., Ritchie, R., Sobey, C. and Miller, A. (2009) Nitroxyl, the novel redox sibling of NO, suppresses cerebrovascular NADPH oxidase. BMC Pharmacology, 9(Suppl), P31. (doi: 10.1186/1471-2210-9-S1-P31) (PMCID:PMC3313343)

Abstract

Background: Nitroxyl (HNO), the reduced and protonated congener of nitric oxide (NO), is emerging as a novel entity with distinct pharmacology and therapeutic advantages over NO• [1]. Importantly, HNO has vasoprotective actions with the potential to serve as an antioxidant. Here we explored the ability of HNO to modulate cerebrovascular NADPH oxidase activity, a major source of superoxide (.O2-) in the vasculature. Materials and methods: Intracranial (pooled middle cerebral and basilar) and extracranial (carotid) cerebral arteries from male C57BL/6J mice were treated with angiotensin II (10 nM) acutely (30 min) and chronically (24 h), respectively, in the absence and presence of the HNO donor, Angeli's salt (AS). NADPH (100 μM)-stimulated .O2- production was then measured using lucigenin (5 μM)-enhanced chemiluminescence. Results: AS (1 μM) did not scavenge .O2- generated in a cell free xanthine (100 μM)/xanthine oxidase (0.05 U/ml) activity assay (control: 447.9 ± 90.8; AS 507.1 ± 113.3 counts, n = 4). In contrast, acute and chronic treatment with AS (0.01–1 μM) caused a concentration-dependent decrease in NADPH oxidase-derived .O2- production by intracranial and extracranial cerebral arteries, respectively (carotid 0.59 ± 0.05; AS 0.1 μM 0.33 ± 0.08; AS 1 μM 0.16 ± 0.03 103 counts/s/mg, P < 0.05, n = 8). The effects of AS were reversed by the HNO scavenger, L-cysteine (3 mM) but unchanged in the presence of the NO• scavenger carboxy-PTIO (200 μM) and sGC inhibitor, ODQ (10 μM). Conclusion: HNO suppresses vascular NADPH-oxidase activity both acutely and chronically, possibly via a cGMP-independent mechanism. Such antioxidant actions of HNO may confer therapeutic advantages in the treatment of cerebrovascular disorders.

• Item Type: Articles
• Additional Information: Conference abstract.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Miller, Dr Alyson
• Authors: Kemp-Harper, B., Ravi, R., Bullen, M., Ritchie, R., Sobey, C., and Miller, A.
• College/School: College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
• Journal Name: BMC Pharmacology
• Publisher: BioMed Central
• ISSN: 1471-2210
• ISSN (Online): 1471-2210
• Copyright Holders: Copyright © 2009 Kemp-Harper et al.