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.
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 language | English |
|---|---|
| Pages (from-to) | 992-997 |
| Number of pages | 6 |
| Journal | Biochemical and Biophysical Research Communications |
| Volume | 499 |
| Issue number | 4 |
| Early online date | 10 Apr 2018 |
| DOIs | |
| Publication status | Published - 23 May 2018 |