The Effects of Diesel Exhaust Inhalation on Vascular Function - the Role of Endothelin

University of Edinburgh

Status: Completed

Conditions: Coronary Disease

Treatments: Drug: BQ-123 and BQ-788; Drug: Endothelin-1

Study type: Interventional

Funder types: Other

Identifiers

NCT00745693

Res08/A116

Details and patient eligibility

About

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

Full 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.

Enrollment: 15 patients

Sex: Male

Ages: 18 to 35 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• Healthy male volunteers

Exclusion criteria

• Use of regular medication
• Cigarette smoking
• Significant occupational exposure to air pollution
• Intercurrent illness

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Triple Blind

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15 participants in 4 patient groups

1

Experimental group

Description:

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)

Treatment:

Drug: Endothelin-1

2

Experimental group

Description:

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

Treatment:

Drug: BQ-123 and BQ-788

3

Experimental group

Description:

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)

Treatment:

Drug: Endothelin-1

4

Experimental group

Description:

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

Treatment:

Drug: BQ-123 and BQ-788