Hany M El-Bassossy1, Thikryat Neamatallah2, Khadijah S Balamash3, Amani T Abushareb3, Malcolm L Watson4. 1. Department of Pharmacology & Toxicology, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia; Department of Pharmacology, Faculty of Pharmacy, Zagazig University, Egypt. Electronic address: helbassossy@kau.edu.sa. 2. Department of Pharmacology & Toxicology, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia. 3. Department of Biochemistry, Faculty of Sciences, King Abdulaziz University, Saudi Arabia. 4. Department of Pharmacy and Pharmacology, University of Bath, UK.
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.
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.
Authors: Zong Xian Zhu; Dan Li Jiang; Bi Jun Li; Hui Qin; Zi Ning Meng; Hao Ran Lin; Jun Hong Xia Journal: Mar Biotechnol (NY) Date: 2019-05-10 Impact factor: 3.619
Authors: Ashraf B Abdel-Naim; Thikryat Neamatallah; Basma G Eid; Ahmed Esmat; Abdulmohsin J Alamoudi; Gamal S Abd El-Aziz; Osama M Ashour Journal: Oxid Med Cell Longev Date: 2018-08-01 Impact factor: 6.543
Authors: Hanan A Henidi; Fahad A Al-Abbasi; Mohamed A El-Moselhy; Hany M El-Bassossy; Ahmed M Al-Abd Journal: Oxid Med Cell Longev Date: 2020-08-07 Impact factor: 6.543
Authors: Hossam M Abdallah; Esraa M Zakaria; Ali M El-Halawany; Gamal A Mohamed; Martin K Safo; Hany M El-Bassossy Journal: PLoS One Date: 2019-09-06 Impact factor: 3.240