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| Name | Class |
|---|---|
| Umeå University | OTHER |
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The purpose of this study is to identify the role of endothelin 1 (a natural vasoconstrictor) in the adverse vascular effects demonstrated after exposure to air pollution
Air pollution is a major problem, and can be linked to around 5% of all deaths worldwide each year. There are strong associations between air pollution exposure and heart disease but we do not yet understand how these harmful effects are mediated. Understanding this mechanism is likely to have a major impact on the way we treat patients with heart disease and have the potential to shape future environmental health policy. The upregulation of Endothelin-1 provides a plausible mechanism for these harmful effects, and we plan to investigate this in more depth in the human forearm following exposure to diesel exhaust.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 1 | Experimental | 1 hour exposure to filtered air, followed by forearm venous occlusion plethysmography at 2 hours after the exposure and infusion of endothelin-1 (5pmol/min) |
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| 2 | Experimental | 1 hour exposure to filtered air, followed by forearm venous occlusion plethysmography at 2 hours after the exposure and infusion of endothelin receptor antagonists BQ-123 and BQ-788 |
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| 3 | Experimental | 1 hour exposure to dilute diesel exhaust (300mcg/m3), followed by forearm venous occlusion plethysmography at 2 hours after the exposure and infusion of endothelin-1 (5pmol/min) |
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| 4 | Experimental | 1 hour exposure to dilute diesel exhaust (300mcg/m3), followed by forearm venous occlusion plethysmography at 2 hours after the exposure and infusion of endothelin receptor antagonists BQ-123 and BQ-788 |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Endothelin-1 | Drug | Intra-arterial infusion of Endothelin-1 at 5pmol/min for 1 hour during venous occlusion plethysmography |
|
| Measure | Description | Time Frame |
|---|---|---|
| Change in forearm blood flow following infusion of endothelin-1 or the endothelin receptor antagonists BQ-123 & BQ-788 | 2 hours after exposure |
| Measure | Description | Time Frame |
|---|---|---|
| 24 hour mean blood pressure (ambulatory monitoring) | 24 hours following the exposure | |
| Systemic endothelin-1 and big endothelin-1 concentrations | At baseline, and immediately, 1, 2, 3, 4, 6 and 24 hours after exposure |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Jeremy P Langrish, MB BCh MRCP | University of Edinburgh | Principal Investigator |
| Anders Blomberg, MD | Umeå University | Study Director |
| Thomas Sandström, MD | Umeå University | Study Director |
| David E Newby, MD FRCP | University of Edinburgh | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Umeå University | Umeå | Västerbottens | SE-901 87 | Sweden |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 16365212 | Background | Mills NL, Tornqvist H, Robinson SD, Gonzalez M, Darnley K, MacNee W, Boon NA, Donaldson K, Blomberg A, Sandstrom T, Newby DE. Diesel exhaust inhalation causes vascular dysfunction and impaired endogenous fibrinolysis. Circulation. 2005 Dec 20;112(25):3930-6. doi: 10.1161/CIRCULATIONAHA.105.588962. | |
| 17446340 | Background |
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| ID | Term |
|---|---|
| D003327 | Coronary Disease |
| ID | Term |
|---|---|
| D017202 | Myocardial Ischemia |
| D006331 | Heart Diseases |
| D002318 | Cardiovascular Diseases |
| D014652 | Vascular Diseases |
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| ID | Term |
|---|---|
| D019332 | Endothelin-1 |
| C072247 | cyclo(Trp-Asp-Pro-Val-Leu) |
| C086539 | BQ 788 |
| ID | Term |
|---|---|
| D016232 | Endothelins |
| D036341 | Intercellular Signaling Peptides and Proteins |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |
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| BQ-123 and BQ-788 | Drug | 1 hour intra-arterial infusion of BQ-123 at 10nmol/min followed by co-infusion of BQ-788 at 1nmol/min for a further hour during forearm venous occlusion plethysmography |
|
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| Changes in arterial stiffness (pulse-wave velocity) | During and for the 1 hour after the exposure |
| Tornqvist H, Mills NL, Gonzalez M, Miller MR, Robinson SD, Megson IL, Macnee W, Donaldson K, Soderberg S, Newby DE, Sandstrom T, Blomberg A. Persistent endothelial dysfunction in humans after diesel exhaust inhalation. Am J Respir Crit Care Med. 2007 Aug 15;176(4):395-400. doi: 10.1164/rccm.200606-872OC. Epub 2007 Apr 19. |
| 17687455 | Background | Calderon-Garciduenas L, Vincent R, Mora-Tiscareno A, Franco-Lira M, Henriquez-Roldan C, Barragan-Mejia G, Garrido-Garcia L, Camacho-Reyes L, Valencia-Salazar G, Paredes R, Romero L, Osnaya H, Villarreal-Calderon R, Torres-Jardon R, Hazucha MJ, Reed W. Elevated plasma endothelin-1 and pulmonary arterial pressure in children exposed to air pollution. Environ Health Perspect. 2007 Aug;115(8):1248-53. doi: 10.1289/ehp.9641. |
| 18629317 | Background | Peretz A, Sullivan JH, Leotta DF, Trenga CA, Sands FN, Allen J, Carlsten C, Wilkinson CW, Gill EA, Kaufman JD. Diesel exhaust inhalation elicits acute vasoconstriction in vivo. Environ Health Perspect. 2008 Jul;116(7):937-42. doi: 10.1289/ehp.11027. |
| 11833973 | Background | Vincent R, Kumarathasan P, Goegan P, Bjarnason SG, Guenette J, Berube D, Adamson IY, Desjardins S, Burnett RT, Miller FJ, Battistini B. Inhalation toxicology of urban ambient particulate matter: acute cardiovascular effects in rats. Res Rep Health Eff Inst. 2001 Oct;(104):5-54; discussion 55-62. |
| 19687345 | Derived | Langrish JP, Lundback M, Mills NL, Johnston NR, Webb DJ, Sandstrom T, Blomberg A, Newby DE. Contribution of endothelin 1 to the vascular effects of diesel exhaust inhalation in humans. Hypertension. 2009 Oct;54(4):910-5. doi: 10.1161/HYPERTENSIONAHA.109.135947. Epub 2009 Aug 17. |
| D011506 | Proteins |
| D001685 | Biological Factors |