Exacerbation of endothelial dysfunction during the progression of diabetes: role of oxidative stress.
To test the deterioration of endothelial function during the progression of diabetes, shear stress-induced dilation (SSID; 10, 20, and 40 dyn/cm(2)) was determined in isolated mesenteric arteries (80-120 μm in diameter) of 6-wk (6W), 3-mo (3M), and 9-mo (9M)-old male db/db mice and their wild-type (...
| Main Authors: | , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
2012
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| _version_ | 1797067245175701504 |
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| author | Huang, A Yang, Y Feher, A Bagi, Z Kaley, G Sun, D |
| author_facet | Huang, A Yang, Y Feher, A Bagi, Z Kaley, G Sun, D |
| author_sort | Huang, A |
| collection | OXFORD |
| description | To test the deterioration of endothelial function during the progression of diabetes, shear stress-induced dilation (SSID; 10, 20, and 40 dyn/cm(2)) was determined in isolated mesenteric arteries (80-120 μm in diameter) of 6-wk (6W), 3-mo (3M), and 9-mo (9M)-old male db/db mice and their wild-type (WT) controls. Nitric oxide (NO)-mediated SSID was comparable in 6W WT and db/db mice, but the dilation was significantly reduced in 3M db/db mice and declined further in 9M db/db mice. Vascular superoxide production was progressively increased in 3M and 9M db/db mice, associated with an increased expression of NADPH oxidase. Inhibition of NADPH oxidase significantly improved NO-mediated SSID in arteries of 3M, but not in 9M, db/db mice. Although endothelial nitric oxide synthase (eNOS) expression was comparable in all groups, a progressive reduction in shear stress-induced eNOS phosphorylation existed in vessels of 3M and 9M db/db mice. Moreover, inducible NOS (iNOS) that was not detected in WT, nor in 6W and 3M db/db mice, was expressed in vessels of 9M db/db mice. A significantly increased expression of nitrotyrosine in total protein and immunoprecipitated eNOS was also found in vessels of 9M db/db mice. Thus, impaired NO bioavailability plays an essential role in the endothelial dysfunction of diabetic mice, which becomes aggravated when endothelial nitrosative stress is further activated via perhaps, an additional iNOS-mediated pathway during the progression of diabetes. |
| first_indexed | 2024-03-06T21:53:37Z |
| format | Journal article |
| id | oxford-uuid:4c26eb3e-00bb-40dd-aed6-b87cd0d26a2c |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T21:53:37Z |
| publishDate | 2012 |
| record_format | dspace |
| spelling | oxford-uuid:4c26eb3e-00bb-40dd-aed6-b87cd0d26a2c2022-03-26T15:47:50ZExacerbation of endothelial dysfunction during the progression of diabetes: role of oxidative stress.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:4c26eb3e-00bb-40dd-aed6-b87cd0d26a2cEnglishSymplectic Elements at Oxford2012Huang, AYang, YFeher, ABagi, ZKaley, GSun, DTo test the deterioration of endothelial function during the progression of diabetes, shear stress-induced dilation (SSID; 10, 20, and 40 dyn/cm(2)) was determined in isolated mesenteric arteries (80-120 μm in diameter) of 6-wk (6W), 3-mo (3M), and 9-mo (9M)-old male db/db mice and their wild-type (WT) controls. Nitric oxide (NO)-mediated SSID was comparable in 6W WT and db/db mice, but the dilation was significantly reduced in 3M db/db mice and declined further in 9M db/db mice. Vascular superoxide production was progressively increased in 3M and 9M db/db mice, associated with an increased expression of NADPH oxidase. Inhibition of NADPH oxidase significantly improved NO-mediated SSID in arteries of 3M, but not in 9M, db/db mice. Although endothelial nitric oxide synthase (eNOS) expression was comparable in all groups, a progressive reduction in shear stress-induced eNOS phosphorylation existed in vessels of 3M and 9M db/db mice. Moreover, inducible NOS (iNOS) that was not detected in WT, nor in 6W and 3M db/db mice, was expressed in vessels of 9M db/db mice. A significantly increased expression of nitrotyrosine in total protein and immunoprecipitated eNOS was also found in vessels of 9M db/db mice. Thus, impaired NO bioavailability plays an essential role in the endothelial dysfunction of diabetic mice, which becomes aggravated when endothelial nitrosative stress is further activated via perhaps, an additional iNOS-mediated pathway during the progression of diabetes. |
| spellingShingle | Huang, A Yang, Y Feher, A Bagi, Z Kaley, G Sun, D Exacerbation of endothelial dysfunction during the progression of diabetes: role of oxidative stress. |
| title | Exacerbation of endothelial dysfunction during the progression of diabetes: role of oxidative stress. |
| title_full | Exacerbation of endothelial dysfunction during the progression of diabetes: role of oxidative stress. |
| title_fullStr | Exacerbation of endothelial dysfunction during the progression of diabetes: role of oxidative stress. |
| title_full_unstemmed | Exacerbation of endothelial dysfunction during the progression of diabetes: role of oxidative stress. |
| title_short | Exacerbation of endothelial dysfunction during the progression of diabetes: role of oxidative stress. |
| title_sort | exacerbation of endothelial dysfunction during the progression of diabetes role of oxidative stress |
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