Endothelial Dysfunction
Conditions
Keywords
Air Pollution, Nitric Oxide, Nitric Oxide Synthase, Diesel exhaust, endothelial dysfunction
Brief summary
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 synthase isoforms (NO) in the adverse vascular responses observed following exposure to diesel exhaust.
Interventions
Forearm venous occlusion plethysmography to measure forearm blood flow during intrabrachial infusion of nitric oxide synthase inhibitors L-NMMA (2-8 µg/min), S-methionyl-L-citrulline (25-200 nmol/min) and 1400W (100-1000 nmol/min) and positive control norepinephrine (60-540 pmol/min)
Sponsors
Study design
Eligibility
Inclusion criteria
* Healthy volunteers
Exclusion criteria
* Regular medication use (except oral contraceptive pill) * Current smokers * Significant occupational exposure to air pollution * Intercurrent illness
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Forearm blood flow measured by venous occlusion plethysmography during intraarterial infusion of nitric oxide synthase inhibitors L-NMMA, SMTC and 1400W and positive control norepinephrine. | 2-4 hours after exposure |
Secondary
| Measure | Time frame |
|---|---|
| Plasma nitrite concentration | During forearm study |
Countries
Sweden