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

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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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Arginase
Advanced Glycosylation End Products
NADPH Oxidase
Vasodilation
Aorta
Rats
Ornithine
Nitric Oxide Synthase Type III
Messenger RNA
Scavenging
Fluorescent Dyes
Superoxides
Acetylcholine
Blood Vessels
Real-Time Polymerase Chain Reaction
Nitric Oxide

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Arginase overexpression and NADPH oxidase stimulation underlie impaired vasodilation induced by advanced glycation end products. / El-bassossy, Hany M; Neamatallah, Thikryat; Balamash, Khadijah S; Abushareb, Amani T; Watson, Malcolm L.

In: Biochemical and Biophysical Research Communications, Vol. 499, No. 4, 23.05.2018, p. 992-997.

Research output: Contribution to journalArticle

El-bassossy, Hany M ; Neamatallah, Thikryat ; Balamash, Khadijah S ; Abushareb, Amani T ; Watson, Malcolm L. / Arginase overexpression and NADPH oxidase stimulation underlie impaired vasodilation induced by advanced glycation end products. In: Biochemical and Biophysical Research Communications. 2018 ; Vol. 499, No. 4. pp. 992-997.
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AU - Abushareb, Amani T

AU - Watson, Malcolm L

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N2 - 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 expressionof 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 butdecreased 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.

AB - 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 expressionof 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 butdecreased 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.

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