L-citrulline increases arginase II protein levels and arginase activity in hypoxic piglet pulmonary artery endothelial cells
The L-arginine precursor, L-citrulline, re-couples endothelial nitric oxide synthase, increases nitric oxide production, and ameliorates chronic hypoxia-induced pulmonary hypertension in newborn pigs. L-arginine can induce arginase, which, in turn, may diminish nitric oxide production. Our major pur...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Wiley
2021-04-01
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| Series: | Pulmonary Circulation |
| Online Access: | https://doi.org/10.1177/20458940211006289 |
| _version_ | 1818235274512039936 |
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| author | Matthew S. Douglass Yongmei Zhang Mark R. Kaplowitz Candice D. Fike |
| author_facet | Matthew S. Douglass Yongmei Zhang Mark R. Kaplowitz Candice D. Fike |
| author_sort | Matthew S. Douglass |
| collection | DOAJ |
| description | The L-arginine precursor, L-citrulline, re-couples endothelial nitric oxide synthase, increases nitric oxide production, and ameliorates chronic hypoxia-induced pulmonary hypertension in newborn pigs. L-arginine can induce arginase, which, in turn, may diminish nitric oxide production. Our major purpose was to determine if L-citrulline increases arginase activity in hypoxic piglet pulmonary arterial endothelial cells, and if so, concomitantly impacts the ability to increase endothelial nitric oxide synthase re-coupling and nitric oxide production. Piglet pulmonary arterial endothelial cells were cultured in hypoxic conditions with L-citrulline (0–3 mM) and/or the arginase inhibitor S-(2-boronoethyl)-L-cysteine. We measured arginase activity and nitric oxide production. We assessed endothelial nitric oxide synthase coupling by measuring endothelial nitric oxide synthase dimers and monomers. L-citrulline concentrations ≥0.5 mM increased arginase activity in hypoxic pulmonary arterial endothelial cells. L-citrulline concentrations ≥0.1 mM increased nitric oxide production and concentrations ≥0.5 mM elevated endothelial nitric oxide synthase dimer-to-monomer ratios. Co-treatment with L-citrulline and S-(2-boronoethyl)-L-cysteine elevated endothelial nitric oxide synthase dimer-to-monomer ratios more than sole treatment. Despite inducing arginase, L-citrulline increased nitric oxide production and endothelial nitric oxide synthase coupling in hypoxic piglet pulmonary arterial endothelial cells. However, these dose-dependent findings raise the possibility that there could be L-citrulline concentrations that elevate arginase to levels that negate improvements in endothelial nitric oxide synthase dysfunction. Moreover, our findings suggest that combining an arginase inhibitor with L-citrulline merits evaluation as a treatment for chronic hypoxia-induced pulmonary hypertension. |
| first_indexed | 2024-12-12T11:51:22Z |
| format | Article |
| id | doaj.art-94e182b8d97041e1bad4d39d69ba826d |
| institution | Directory Open Access Journal |
| issn | 2045-8940 |
| language | English |
| last_indexed | 2024-12-12T11:51:22Z |
| publishDate | 2021-04-01 |
| publisher | Wiley |
| record_format | Article |
| series | Pulmonary Circulation |
| spelling | doaj.art-94e182b8d97041e1bad4d39d69ba826d2022-12-22T00:25:18ZengWileyPulmonary Circulation2045-89402021-04-011110.1177/20458940211006289L-citrulline increases arginase II protein levels and arginase activity in hypoxic piglet pulmonary artery endothelial cellsMatthew S. DouglassYongmei ZhangMark R. KaplowitzCandice D. FikeThe L-arginine precursor, L-citrulline, re-couples endothelial nitric oxide synthase, increases nitric oxide production, and ameliorates chronic hypoxia-induced pulmonary hypertension in newborn pigs. L-arginine can induce arginase, which, in turn, may diminish nitric oxide production. Our major purpose was to determine if L-citrulline increases arginase activity in hypoxic piglet pulmonary arterial endothelial cells, and if so, concomitantly impacts the ability to increase endothelial nitric oxide synthase re-coupling and nitric oxide production. Piglet pulmonary arterial endothelial cells were cultured in hypoxic conditions with L-citrulline (0–3 mM) and/or the arginase inhibitor S-(2-boronoethyl)-L-cysteine. We measured arginase activity and nitric oxide production. We assessed endothelial nitric oxide synthase coupling by measuring endothelial nitric oxide synthase dimers and monomers. L-citrulline concentrations ≥0.5 mM increased arginase activity in hypoxic pulmonary arterial endothelial cells. L-citrulline concentrations ≥0.1 mM increased nitric oxide production and concentrations ≥0.5 mM elevated endothelial nitric oxide synthase dimer-to-monomer ratios. Co-treatment with L-citrulline and S-(2-boronoethyl)-L-cysteine elevated endothelial nitric oxide synthase dimer-to-monomer ratios more than sole treatment. Despite inducing arginase, L-citrulline increased nitric oxide production and endothelial nitric oxide synthase coupling in hypoxic piglet pulmonary arterial endothelial cells. However, these dose-dependent findings raise the possibility that there could be L-citrulline concentrations that elevate arginase to levels that negate improvements in endothelial nitric oxide synthase dysfunction. Moreover, our findings suggest that combining an arginase inhibitor with L-citrulline merits evaluation as a treatment for chronic hypoxia-induced pulmonary hypertension.https://doi.org/10.1177/20458940211006289 |
| spellingShingle | Matthew S. Douglass Yongmei Zhang Mark R. Kaplowitz Candice D. Fike L-citrulline increases arginase II protein levels and arginase activity in hypoxic piglet pulmonary artery endothelial cells Pulmonary Circulation |
| title | L-citrulline increases arginase II protein levels and arginase activity in hypoxic piglet pulmonary artery endothelial cells |
| title_full | L-citrulline increases arginase II protein levels and arginase activity in hypoxic piglet pulmonary artery endothelial cells |
| title_fullStr | L-citrulline increases arginase II protein levels and arginase activity in hypoxic piglet pulmonary artery endothelial cells |
| title_full_unstemmed | L-citrulline increases arginase II protein levels and arginase activity in hypoxic piglet pulmonary artery endothelial cells |
| title_short | L-citrulline increases arginase II protein levels and arginase activity in hypoxic piglet pulmonary artery endothelial cells |
| title_sort | l citrulline increases arginase ii protein levels and arginase activity in hypoxic piglet pulmonary artery endothelial cells |
| url | https://doi.org/10.1177/20458940211006289 |
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