Arginase 1 contributes to diminished coronary arteriolar dilation in patients with diabetes.
Arginase 1, via competing with nitric oxide (NO) synthase for the substrate L-arginine, may interfere with NO-mediated vascular responses. We tested the hypothesis that arginase 1 contributes to coronary vasomotor dysfunction in patients with diabetes mellitus (DM). Coronary arterioles were dissecte...
| Hlavní autoři: | , , , , |
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| Médium: | Journal article |
| Jazyk: | English |
| Vydáno: |
2011
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| _version_ | 1826289662092640256 |
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| author | Beleznai, T Feher, A Spielvogel, D Lansman, S Bagi, Z |
| author_facet | Beleznai, T Feher, A Spielvogel, D Lansman, S Bagi, Z |
| author_sort | Beleznai, T |
| collection | OXFORD |
| description | Arginase 1, via competing with nitric oxide (NO) synthase for the substrate L-arginine, may interfere with NO-mediated vascular responses. We tested the hypothesis that arginase 1 contributes to coronary vasomotor dysfunction in patients with diabetes mellitus (DM). Coronary arterioles were dissected from the right atrial appendages of 41 consecutive patients with or without DM (the 2 groups suffered from similar comorbidities), and agonist-induced changes in diameter were measured with videomicroscopy. We found that the endothelium-dependent agonist ACh elicited a diminished vasodilation and caused constriction to the highest ACh concentration (0.1 μM) with a similar magnitude in patients with (18 ± 8%) and without (17 ± 9%) DM. Responses to ACh were not significantly affected by the inhibition of NO synthesis with N(G)-nitro-L-arginine methyl ester in either group. The NO donor sodium nitroprusside-dependent dilations were not different in patients with or without DM. Interestingly, we found that the presence of N(G)-hydroxy-L-arginine (10 μM), a selective inhibitor of arginase or application of L-arginine (3 mM), restored ACh-induced coronary dilations only in patients with DM (to 47 ± 6% and to 40 ± 19%, respectively) but not in subjects without DM. Correspondingly, the protein expression of arginase 1 was increased in coronary arterioles of patients with DM compared with subjects without diabetes. Moreover, using immunocytochemistry, we detected an abundant immunostaining of arginase 1 in coronary endothelial cells of patients with DM, which was colocalized with NO synthase. Collectively, we provided evidence for a distinct upregulation of arginase 1 in coronary arterioles of patients with DM, which contributes to a reduced NO production and consequently diminished vasodilation. |
| first_indexed | 2024-03-07T02:32:18Z |
| format | Journal article |
| id | oxford-uuid:a7a6e609-885c-4bba-a3eb-4685e29b4743 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T02:32:18Z |
| publishDate | 2011 |
| record_format | dspace |
| spelling | oxford-uuid:a7a6e609-885c-4bba-a3eb-4685e29b47432022-03-27T02:56:02ZArginase 1 contributes to diminished coronary arteriolar dilation in patients with diabetes.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:a7a6e609-885c-4bba-a3eb-4685e29b4743EnglishSymplectic Elements at Oxford2011Beleznai, TFeher, ASpielvogel, DLansman, SBagi, ZArginase 1, via competing with nitric oxide (NO) synthase for the substrate L-arginine, may interfere with NO-mediated vascular responses. We tested the hypothesis that arginase 1 contributes to coronary vasomotor dysfunction in patients with diabetes mellitus (DM). Coronary arterioles were dissected from the right atrial appendages of 41 consecutive patients with or without DM (the 2 groups suffered from similar comorbidities), and agonist-induced changes in diameter were measured with videomicroscopy. We found that the endothelium-dependent agonist ACh elicited a diminished vasodilation and caused constriction to the highest ACh concentration (0.1 μM) with a similar magnitude in patients with (18 ± 8%) and without (17 ± 9%) DM. Responses to ACh were not significantly affected by the inhibition of NO synthesis with N(G)-nitro-L-arginine methyl ester in either group. The NO donor sodium nitroprusside-dependent dilations were not different in patients with or without DM. Interestingly, we found that the presence of N(G)-hydroxy-L-arginine (10 μM), a selective inhibitor of arginase or application of L-arginine (3 mM), restored ACh-induced coronary dilations only in patients with DM (to 47 ± 6% and to 40 ± 19%, respectively) but not in subjects without DM. Correspondingly, the protein expression of arginase 1 was increased in coronary arterioles of patients with DM compared with subjects without diabetes. Moreover, using immunocytochemistry, we detected an abundant immunostaining of arginase 1 in coronary endothelial cells of patients with DM, which was colocalized with NO synthase. Collectively, we provided evidence for a distinct upregulation of arginase 1 in coronary arterioles of patients with DM, which contributes to a reduced NO production and consequently diminished vasodilation. |
| spellingShingle | Beleznai, T Feher, A Spielvogel, D Lansman, S Bagi, Z Arginase 1 contributes to diminished coronary arteriolar dilation in patients with diabetes. |
| title | Arginase 1 contributes to diminished coronary arteriolar dilation in patients with diabetes. |
| title_full | Arginase 1 contributes to diminished coronary arteriolar dilation in patients with diabetes. |
| title_fullStr | Arginase 1 contributes to diminished coronary arteriolar dilation in patients with diabetes. |
| title_full_unstemmed | Arginase 1 contributes to diminished coronary arteriolar dilation in patients with diabetes. |
| title_short | Arginase 1 contributes to diminished coronary arteriolar dilation in patients with diabetes. |
| title_sort | arginase 1 contributes to diminished coronary arteriolar dilation in patients with diabetes |
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