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| Name | Class |
|---|---|
| Umeå University | OTHER |
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Exposure to air pollution has been linked to increased cardiorespiratory morbidity and mortality. The exact component of air pollution that mediates this effect is unknown, but the link is strongest for fine combustion derived particulate matter derived from traffic sources. Recently, it has been demonstrated that inhalation of diesel exhaust impairs vascular vasomotor tone and endogenous fibrinolysis. The mechanism underlying these detrimental vascular is unclear, but is thought to be via oxidative stress and altered bioavailability of endogenous nitric oxide. In these studies we plan to elucidate the role of endogenous nitric oxide (NO) in the adverse vascular responses observed following exposure to diesel exhaust.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Diesel Exposure | Experimental | 1 hour exposure to dilute diesel exhaust at a concentration of 300 µg/m3 with intermittent exercise |
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| Air Exposure | Experimental | 1 hour exposure to filtered air during intermittent exercise |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Forearm Vascular Study | Procedure | Forearm venous occlusion plethysmography during intraarterial infusion of L-NMMA (2-8 µmol/min) followed by co-infusion of sodium nitroprusside (90-900 ng/min) as a "nitric oxide clamp". Forearm blood flow then measured during the clamp in response to infused vasodilators acetylcholine (5-20 mg/min), bradykinin (100-1000 pmol/min), verapamil (10-100 µg/min) and sodium nitroprusside (2-8 µg/min). |
| Measure | Description | Time Frame |
|---|---|---|
| Forearm blood flow as measured by venous occlusion plethysmography during infusion of NOS inhibitors and vasodilators | 2-4 hours after exposure |
| Measure | Description | Time Frame |
|---|---|---|
| Plasma nitrite concentrations | During forearm study | |
| Plasma concentrations of t-PA and PAI | After infusion of bradykinin during forearm study |
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| Name | Affiliation | Role |
|---|---|---|
| Anders Blomberg, MD PhD | Umeå University | Principal Investigator |
| David E Newby, PhD FRCP | University of Edinburgh | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Umeå University | Umeå | 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. | |
| 23525434 | Derived |
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| Langrish JP, Unosson J, Bosson J, Barath S, Muala A, Blackwell S, Soderberg S, Pourazar J, Megson IL, Treweeke A, Sandstrom T, Newby DE, Blomberg A, Mills NL. Altered nitric oxide bioavailability contributes to diesel exhaust inhalation-induced cardiovascular dysfunction in man. J Am Heart Assoc. 2013 Feb 19;2(1):e004309. doi: 10.1161/JAHA.112.004309. |