Arginase overexpression and NADPH oxidase stimulation underlie impaired vasodilation induced by advanced glycation end products

Hany M El-bassossy, Thikryat Neamatallah, Khadijah S Balamash, Amani T Abushareb, Malcolm L Watson

Research output: Contribution to journalArticle

6 Citations (Scopus)
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Abstract

Background: Advanced glycation endproducts (AGEs) play a major role in the development of many vascular complications that are mediated by endothelial dysfunction. The present work aimed to investigate the mechanism by which AGEs impair vasodilation.
Methods: The effect of AGEs on vasodilation induced by acetylcholine or D NONOate was examined by incubating isolated rat aortae with different AGEs concentrations. ACh-induced nitric oxide generation was assessed using the fluorescent probe diaminofluorecein (DAF-FM). The effect of AGEs on expression
of mRNA for arginase 2, NADPH oxidase and endothelial nitric oxide synthase (eNOS) were determined by real-time PCR.
Results: One-hour in vitro incubation of rat aortae with AGEs impaired endothelial-dependent vasodilation produced by ACh, while increasing D NONOate-induced vasodilation. Preincubation of aortae with L-ornithine, an arginase 2-inhibitor, prevented the impairment effect induced by AGEs on endothelial dependent vasodilation. Superoxide scavenging by tempol or NADPH oxidase inhibition by apocynin also blocked the effect of AGEs. AGEs decreased ACh-induced NO production and this was inhibited by both L-ornithine and apocynin. Furthermore, AGEs exposure increased arginase mRNA expression but
decreased mRNA expression for eNOS in isolated rat aortae.
Conclusion: The present results indicate that AGEs impairs endothelial-dependent vasodilation, and this effect is mediated via arginase overexpression and NADPH oxidase stimulation.
Original languageEnglish
Pages (from-to)992-997
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume499
Issue number4
Early online date10 Apr 2018
DOIs
Publication statusPublished - 23 May 2018

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