Inflammation-induced endothelial dysfunction involves reduced nitric oxide bioavailability and increased oxidant stress.
OBJECTIVES: Our aim was to investigate mechanisms of inflammation-induced endothelial dysfunction in humans. METHODS: Endothelial function in twenty-one healthy human volunteers was measured using forearm venous plethysmography before and 8 h after administration of typhoid vaccination to generate...
| Main Authors: | , , , , , , |
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| Format: | Journal article |
| Language: | English |
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2004
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| _version_ | 1826274189462470656 |
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| author | Clapp, B Hingorani, A Kharbanda, R Mohamed-Ali, V Stephens, J Vallance, P MacAllister, R |
| author_facet | Clapp, B Hingorani, A Kharbanda, R Mohamed-Ali, V Stephens, J Vallance, P MacAllister, R |
| author_sort | Clapp, B |
| collection | OXFORD |
| description | OBJECTIVES: Our aim was to investigate mechanisms of inflammation-induced endothelial dysfunction in humans. METHODS: Endothelial function in twenty-one healthy human volunteers was measured using forearm venous plethysmography before and 8 h after administration of typhoid vaccination to generate an inflammatory response. Basal and stimulated endothelial nitric oxide (NO) bioavailability was assessed by measurement of the responses to intra-arterial N(G)-monomethyl-l-arginine (l-NMMA) and bradykinin, respectively. The effects of supplementation with l-arginine or ascorbic acid were assessed to probe the effects of substrate deficiency and oxidative stress, respectively. Systemic effects were determined by measuring cytokine response, total anti-oxidant status (TAOS) and urinary protein excretion. RESULTS: Vaccination induced a cytokine response, a fall in total anti-oxidant status and increased urinary albumin excretion (UAE). There was a reduction in the response to bradykinin (BK, P<0.005) and l-NMMA (P<0.0001) with no effect on the response to glyceryl trinitrate (GTN) and norepinephrine (NE). Following vaccination blood flow response to BK (but not GTN) was partially returned to pre-vaccine levels by infusion of ascorbic acid (P=0.01). Supplementation with l-arginine had no effect. CONCLUSION: Inflammation causes widespread endothelial dysfunction, reduces vascular NO bioavailability and increases oxidative stress. These actions are partially reversible with local anti-oxidants. These findings suggest a role for reactive oxygen species in inflammation-induced endothelial dysfunction. |
| first_indexed | 2024-03-06T22:39:40Z |
| format | Journal article |
| id | oxford-uuid:5b1c335b-fef3-4a99-a26e-677419143b3c |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T22:39:40Z |
| publishDate | 2004 |
| record_format | dspace |
| spelling | oxford-uuid:5b1c335b-fef3-4a99-a26e-677419143b3c2022-03-26T17:20:02ZInflammation-induced endothelial dysfunction involves reduced nitric oxide bioavailability and increased oxidant stress.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:5b1c335b-fef3-4a99-a26e-677419143b3cEnglishSymplectic Elements at Oxford2004Clapp, BHingorani, AKharbanda, RMohamed-Ali, VStephens, JVallance, PMacAllister, R OBJECTIVES: Our aim was to investigate mechanisms of inflammation-induced endothelial dysfunction in humans. METHODS: Endothelial function in twenty-one healthy human volunteers was measured using forearm venous plethysmography before and 8 h after administration of typhoid vaccination to generate an inflammatory response. Basal and stimulated endothelial nitric oxide (NO) bioavailability was assessed by measurement of the responses to intra-arterial N(G)-monomethyl-l-arginine (l-NMMA) and bradykinin, respectively. The effects of supplementation with l-arginine or ascorbic acid were assessed to probe the effects of substrate deficiency and oxidative stress, respectively. Systemic effects were determined by measuring cytokine response, total anti-oxidant status (TAOS) and urinary protein excretion. RESULTS: Vaccination induced a cytokine response, a fall in total anti-oxidant status and increased urinary albumin excretion (UAE). There was a reduction in the response to bradykinin (BK, P<0.005) and l-NMMA (P<0.0001) with no effect on the response to glyceryl trinitrate (GTN) and norepinephrine (NE). Following vaccination blood flow response to BK (but not GTN) was partially returned to pre-vaccine levels by infusion of ascorbic acid (P=0.01). Supplementation with l-arginine had no effect. CONCLUSION: Inflammation causes widespread endothelial dysfunction, reduces vascular NO bioavailability and increases oxidative stress. These actions are partially reversible with local anti-oxidants. These findings suggest a role for reactive oxygen species in inflammation-induced endothelial dysfunction. |
| spellingShingle | Clapp, B Hingorani, A Kharbanda, R Mohamed-Ali, V Stephens, J Vallance, P MacAllister, R Inflammation-induced endothelial dysfunction involves reduced nitric oxide bioavailability and increased oxidant stress. |
| title | Inflammation-induced endothelial dysfunction involves reduced nitric oxide bioavailability and increased oxidant stress. |
| title_full | Inflammation-induced endothelial dysfunction involves reduced nitric oxide bioavailability and increased oxidant stress. |
| title_fullStr | Inflammation-induced endothelial dysfunction involves reduced nitric oxide bioavailability and increased oxidant stress. |
| title_full_unstemmed | Inflammation-induced endothelial dysfunction involves reduced nitric oxide bioavailability and increased oxidant stress. |
| title_short | Inflammation-induced endothelial dysfunction involves reduced nitric oxide bioavailability and increased oxidant stress. |
| title_sort | inflammation induced endothelial dysfunction involves reduced nitric oxide bioavailability and increased oxidant stress |
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