Coronary Disease
Conditions
Keywords
Endothelin, Air pollution, Diesel exhaust, Vascular function, exposure
Brief summary
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
Detailed description
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.
Interventions
DRUGEndothelin-1
Intra-arterial infusion of Endothelin-1 at 5pmol/min for 1 hour during venous occlusion plethysmography
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
Sponsors
Umeå University
University of Edinburgh
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
MALE
Age
18 Years to 35 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy male volunteers
Exclusion criteria
* Use of regular medication * Cigarette smoking * Significant occupational exposure to air pollution * Intercurrent illness
Design outcomes
Primary
| Measure | 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 |
Secondary
| Measure | 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 |
| Changes in arterial stiffness (pulse-wave velocity) | During and for the 1 hour after the exposure |
Countries
Sweden
Outcome results
None listed