Role of Nox inhibitors plumbagin, ML090 and gp91ds-tat peptide on homocysteine thiolactone induced XXXX .

@entity71837 @entity95 @entity52881 @entity1503 @entity52880 @entity65
UNASSIGNED: Antioxidants have not reduced the burden of @entity65 , and current evidence suggests a beneficial role of oxidative stress, via NADPH oxidase (Nox) upregulation, in endothelial function. Homocysteine thiolactone (HcyT) induces @entity1503 and this correlates with increased vascular oxidative stress. AIMS: To determine if pharmacological inhibition of Nox could impair @entity1503 . METHODS: Abdominal aorta were excised from New Zealand White @entity95 (n=6), cut into rings and sequentially mounted in organ baths. Rings were preincubated with 0.55 M homocysteine thiolactone for 1hr, or combinations of putative Nox inhibitors (plumbagin for @entity52881 , gp91ds-tat for @entity71837 , and ML090 for @entity52880 ), 30 minutes prior to the addition of HcyT, followed by a dose response curve to acetylcholine on phenylephrine preconstricted rings. RESULTS: Plumbagin, ML090 + gp91ds-tat and HcyT reduced responses to acetylcholine, and Plumbagin + Hcyt caused constriction to acetylcholine, which was normalised to plumbagin by ML090. Plumbagin + ML090 or plumbagin + gp91ds-tat completely impaired the effect of acetylcholine. ML090 inhibited the effect of HcyT on reduced response to acetylcholine, whereas gp91ds-tat had no effect. CONCLUSION: Inhibition of @entity52880 prevents, whereas inhibition of @entity52881 worsens acetylcholine induced blood vessel relaxation caused by HcyT, while @entity71837 inhibition has no effect. However combinations of Nox inhibitors worsen acetylcholine induced blood vessel relaxation. These results suggest that there is cross-talk between Nox isoforms during physiological and pathophysiological processes. This article is protected by copyright. All rights reserved.
