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Vascular nitric oxide resistance in type 2 diabetes
Vascular nitric oxide (NO•) resistance, manifested by an impaired vasodilator function of NO• in both the macro- and microvessels, is a common state in type 2 diabetes (T2D) associated with developing cardiovascular events and death. Here, we summarize experimental and human evidence of vascular NO•...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Nature Publishing Group UK
2023
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10336063/ https://www.ncbi.nlm.nih.gov/pubmed/37433795 http://dx.doi.org/10.1038/s41419-023-05935-5 |
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author | Bahadoran, Zahra Mirmiran, Parvin Kashfi, Khosrow Ghasemi, Asghar |
author_facet | Bahadoran, Zahra Mirmiran, Parvin Kashfi, Khosrow Ghasemi, Asghar |
author_sort | Bahadoran, Zahra |
collection | PubMed |
description | Vascular nitric oxide (NO•) resistance, manifested by an impaired vasodilator function of NO• in both the macro- and microvessels, is a common state in type 2 diabetes (T2D) associated with developing cardiovascular events and death. Here, we summarize experimental and human evidence of vascular NO• resistance in T2D and discuss its underlying mechanisms. Human studies indicate a ~ 13-94% decrease in the endothelium (ET)-dependent vascular smooth muscle (VSM) relaxation and a 6-42% reduced response to NO• donors, i.e., sodium nitroprusside (SNP) and glyceryl trinitrate (GTN), in patients with T2D. A decreased vascular NO• production, NO• inactivation, and impaired responsiveness of VSM to NO• [occurred due to quenching NO• activity, desensitization of its receptor soluble guanylate cyclase (sGC), and/or impairment of its downstream pathway, cyclic guanosine monophosphate (cGMP)-protein kinase G (PKG)] are the known mechanisms underlying the vascular NO• resistance in T2D. Hyperglycemia-induced overproduction of reactive oxygen species (ROS) and vascular insulin resistance are key players in this state. Therefore, upregulating vascular NO• availability, re-sensitizing or bypassing the non-responsive pathways to NO•, and targeting key vascular sources of ROS production may be clinically relevant pharmacological approaches to circumvent T2D-induced vascular NO• resistance. |
format | Online Article Text |
id | pubmed-10336063 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-103360632023-07-13 Vascular nitric oxide resistance in type 2 diabetes Bahadoran, Zahra Mirmiran, Parvin Kashfi, Khosrow Ghasemi, Asghar Cell Death Dis Review Article Vascular nitric oxide (NO•) resistance, manifested by an impaired vasodilator function of NO• in both the macro- and microvessels, is a common state in type 2 diabetes (T2D) associated with developing cardiovascular events and death. Here, we summarize experimental and human evidence of vascular NO• resistance in T2D and discuss its underlying mechanisms. Human studies indicate a ~ 13-94% decrease in the endothelium (ET)-dependent vascular smooth muscle (VSM) relaxation and a 6-42% reduced response to NO• donors, i.e., sodium nitroprusside (SNP) and glyceryl trinitrate (GTN), in patients with T2D. A decreased vascular NO• production, NO• inactivation, and impaired responsiveness of VSM to NO• [occurred due to quenching NO• activity, desensitization of its receptor soluble guanylate cyclase (sGC), and/or impairment of its downstream pathway, cyclic guanosine monophosphate (cGMP)-protein kinase G (PKG)] are the known mechanisms underlying the vascular NO• resistance in T2D. Hyperglycemia-induced overproduction of reactive oxygen species (ROS) and vascular insulin resistance are key players in this state. Therefore, upregulating vascular NO• availability, re-sensitizing or bypassing the non-responsive pathways to NO•, and targeting key vascular sources of ROS production may be clinically relevant pharmacological approaches to circumvent T2D-induced vascular NO• resistance. Nature Publishing Group UK 2023-07-11 /pmc/articles/PMC10336063/ /pubmed/37433795 http://dx.doi.org/10.1038/s41419-023-05935-5 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Review Article Bahadoran, Zahra Mirmiran, Parvin Kashfi, Khosrow Ghasemi, Asghar Vascular nitric oxide resistance in type 2 diabetes |
title | Vascular nitric oxide resistance in type 2 diabetes |
title_full | Vascular nitric oxide resistance in type 2 diabetes |
title_fullStr | Vascular nitric oxide resistance in type 2 diabetes |
title_full_unstemmed | Vascular nitric oxide resistance in type 2 diabetes |
title_short | Vascular nitric oxide resistance in type 2 diabetes |
title_sort | vascular nitric oxide resistance in type 2 diabetes |
topic | Review Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10336063/ https://www.ncbi.nlm.nih.gov/pubmed/37433795 http://dx.doi.org/10.1038/s41419-023-05935-5 |
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