Cyclooxygenase-2 Inhibition Limits Angiotensin II-Induced DNA Oxidation and Protein Nitration in Humans
| Autor: | Erica N. Chirico, Marc J. Poulin, Darlene Y. Sola, Brenda R. Hemmelgarn, Camille Faes, Daniel A. Muruve, Sofia B. Ahmed, Vincent Pialoux |
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| Přispěvatelé: | Laboratoire Interuniversitaire de Biologie de la Motricité (LIBM ), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry]), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM), Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National de la Recherche Agronomique (INRA) |
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty Physiology renin-angiotensin system 030204 cardiovascular system & hematology medicine.disease_cause Nitric oxide 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine nitric oxide Physiology (medical) Internal medicine Renin–angiotensin system medicine oxidative stress humans ComputingMilieux_MISCELLANEOUS Original Research Angiotensin II receptor type 1 celecoxib biology Nitrotyrosine blood pressure Angiotensin-converting enzyme Angiotensin II cycloxygenase-2 inhibition 3. Good health [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry Molecular Biology/Biomolecules [q-bio.BM] 030104 developmental biology Endocrinology chemistry Advanced oxidation protein products endothelin-1 biology.protein Oxidative stress |
| Zdroj: | Frontiers in Physiology Frontiers in Physiology, Frontiers, 2017, 8, ⟨10.3389/fphys.2017.00138⟩ |
| ISSN: | 1664-042X |
| Popis: | Compared to other cyclooxygenase-2 inhibitors, celecoxib is associated with a lower cardiovascular risk, though the mechanism remains unclear. Angiotensin II is an important mediator of oxidative stress in the pathophysiology of vascular disease. Cyclooxygenase-2 may modify the effects of angiotensin II though this has never been studied in humans. The purpose of the study was to test the effects of selective cyclooxygenase-2 inhibition on plasma measures of oxidative stress, the vasoconstrictor endothelin-1, and nitric oxide metabolites, both at baseline and in respose to Angiotensin II challenge in healthy humans. Measures of 8-hydroxydeoxyguanosine, advanced oxidation protein products, nitrotyrosine, endothelin-1, and nitric oxide metabolites were assessed from plasma samples drawn at baseline and in response to graded angiotensin II infusion (3 ng/kg/min × 30 min, 6 ng/kg/min × 30 min) before and after 14 days of cyclooxygenase-2 inhibition in 14 healthy subjects (eight male, six female) in high salt balance, a state of maximal renin angiotensin system suppression. Angiotensin II infusion significantly increased plasma oxidative stress compared to baseline (8-hydroxydeoxyguanosine; +17%; advanced oxidation protein products; +16%), nitrotyrosine (+76%). Furthermore, levels of endothelin-1 levels were significantly increased (+115%) and nitric oxide metabolites were significantly decreased (−20%). Cycloxygenase-2 inhibition significantly limited the increase in 8-hydroxydeoxyguanosine, nitrotyrosine and the decrease in nitric oxide metabolites induced by angiotensin II infusion, though no changes in advanced oxidation protein products and endothelin-1 concentrations were observed. Cyclooxygenase-2 inhibition with celecoxib partially limited the angiotensin II-mediated increases in markers of oxidative stress in humans, offering a potential physiological pathway for the improved cardiovascular risk profile of this drug. |
| Databáze: | OpenAIRE |
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