Nadim Naser, Chenchel K. Lonj, Matthew Rikard-Bell, Shaun L. Sandow, Timothy V. Murphy
{"title":"晚期糖基化终产物通过构成性内皮RAGE和Nox1/4抑制大鼠离体骨骼肌动脉的扩张。","authors":"Nadim Naser, Chenchel K. Lonj, Matthew Rikard-Bell, Shaun L. Sandow, Timothy V. Murphy","doi":"10.1111/micc.12837","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <h3> Objective</h3>\n \n <p>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).</p>\n </section>\n \n <section>\n \n <h3> Methods</h3>\n \n <p>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.</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>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.</p>\n </section>\n \n <section>\n \n <h3> Conclusion</h3>\n \n <p>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.</p>\n </section>\n </div>","PeriodicalId":18459,"journal":{"name":"Microcirculation","volume":null,"pages":null},"PeriodicalIF":1.9000,"publicationDate":"2023-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/micc.12837","citationCount":"0","resultStr":"{\"title\":\"Advanced glycated end-products inhibit dilation through constitutive endothelial RAGE and Nox1/4 in rat isolated skeletal muscle arteries\",\"authors\":\"Nadim Naser, Chenchel K. Lonj, Matthew Rikard-Bell, Shaun L. Sandow, Timothy V. Murphy\",\"doi\":\"10.1111/micc.12837\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div>\\n \\n \\n <section>\\n \\n <h3> Objective</h3>\\n \\n <p>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).</p>\\n </section>\\n \\n <section>\\n \\n <h3> Methods</h3>\\n \\n <p>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.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Results</h3>\\n \\n <p>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.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Conclusion</h3>\\n \\n <p>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.</p>\\n </section>\\n </div>\",\"PeriodicalId\":18459,\"journal\":{\"name\":\"Microcirculation\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":1.9000,\"publicationDate\":\"2023-11-20\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://onlinelibrary.wiley.com/doi/epdf/10.1111/micc.12837\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Microcirculation\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1111/micc.12837\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"HEMATOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Microcirculation","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1111/micc.12837","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"HEMATOLOGY","Score":null,"Total":0}
Advanced glycated end-products inhibit dilation through constitutive endothelial RAGE and Nox1/4 in rat isolated skeletal muscle arteries
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.
期刊介绍:
The journal features original contributions that are the result of investigations contributing significant new information relating to the vascular and lymphatic microcirculation addressed at the intact animal, organ, cellular, or molecular level. Papers describe applications of the methods of physiology, biophysics, bioengineering, genetics, cell biology, biochemistry, and molecular biology to problems in microcirculation.
Microcirculation also publishes state-of-the-art reviews that address frontier areas or new advances in technology in the fields of microcirculatory disease and function. Specific areas of interest include: Angiogenesis, growth and remodeling; Transport and exchange of gasses and solutes; Rheology and biorheology; Endothelial cell biology and metabolism; Interactions between endothelium, smooth muscle, parenchymal cells, leukocytes and platelets; Regulation of vasomotor tone; and Microvascular structures, imaging and morphometry. Papers also describe innovations in experimental techniques and instrumentation for studying all aspects of microcirculatory structure and function.