Advanced glycated end-products inhibit dilation through constitutive endothelial RAGE and Nox1/4 in rat isolated skeletal muscle arteries

Nadim Naser; Chenchel K Lonj; Matthew Rikard-Bell; Shaun L Sandow; Timothy V Murphy

doi:10.1111/micc.12837

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Advanced glycated end-products inhibit dilation through constitutive endothelial RAGE and Nox1/4 in rat isolated skeletal muscle arteries

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Advanced glycated end-products inhibit dilation through constitutive endothelial RAGE and Nox1/4 in rat isolated skeletal muscle arteries

Nadim Naser, Chenchel K Lonj, Matthew Rikard-Bell, Shaun L Sandow and Timothy V Murphy

Microcirculation, Vol.31(1), pp.1-14

2024

DOI: https://doi.org/10.1111/micc.12837

PMID: 37985248

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Abstract

advanced glycated end-products

artery

endothelium

endothelium-dependent dilation

NAD(P)H oxidase

smooth muscle

Objective: This study investigated the actions of advanced glycated end-products (AGE), their receptors (RAGE), and NAD(P)H oxidase (Nox) subtypes 1, 2, and 4 on mechanisms of endothelium-dependent dilation of the rat cremaster muscle artery (CMA). Methods: Immunofluorescence studies were used to examine expression of RAGE in rat arteries. ROS accumulation was measured using luminescence and fluorescence assays. Functional studies were performed using pressure myography. Results: High levels of RAGE expression were shown in the endothelial cells of the CMA, compared with low endothelial expression in middle cerebral and mesenteric arteries and the aorta. Exogenous AGE (in vitro glycated bovine serum albumin) stimulated H2O2 accumulation in CMA, which was prevented by the RAGE antagonist FPS-ZM1, the NAD(P)H oxidase (Nox) inhibitor apocynin and inhibited by the Nox1/4 inhibitor setanaxib, but not the Nox2 inhibitor GSK2795039. In functional studies, AGE inhibited vasodilation of CMA stimulated by acetylcholine, sodium nitroprusside, and the BKCa activator NS1619, but not adenosine-induced dilation. FPS-ZM1, apocynin, and setanaxib prevented the inhibitory effects of AGE on responses to acetylcholine and NS-1619. Conclusion: These observations suggest RAGE are constitutively expressed in the endothelium of the rat CMA and may be activated by AGE to stimulate Nox1/4 and ROS formation with resulting inhibition of NO and BKCa-mediated endothelium-dependent dilation.

Details

Title: Advanced glycated end-products inhibit dilation through constitutive endothelial RAGE and Nox1/4 in rat isolated skeletal muscle arteries
Authors: Nadim Naser (Author) - UNSW Sydney
Chenchel K Lonj (Author) - UNSW Sydney
Matthew Rikard-Bell (Author) - UNSW Sydney
Shaun L Sandow (Author) - University of the Sunshine Coast, Queensland, School of Health - Biomedicine
Timothy V Murphy (Corresponding Author) - UNSW Sydney
Publication details: Microcirculation, Vol.31(1), pp.1-14
Publisher: John Wiley & Sons Ltd.
Date published: 2024
DOI: 10.1111/micc.12837
ISSN: 1549-8719
PMID: 37985248
Copyright note: © 2023 The Authors. Microcirculation published by John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Grant note: National Heart Foundation of Australia
Organisation Unit: School of Health - Biomedicine; Healthy Ageing Research Cluster
Language: English
Record Identifier: 99980396302621
Output Type: Journal article

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