The Cardiovascular Effects of Air Pollution: the Role of Nitric Oxide

Study Overview
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Brief Summary
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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.

Official Title
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The Cardiovascular Effects of Air Pollution: the Role of Nitric Oxide

Conditions
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Endothelial Dysfunction

Intervention / Treatment
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* Procedure: Forearm Vascular Study


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy volunteers Exclusion Criteria: Use of regular medication (except oral contraceptive pill) Current smokers Significant occupational exposure to air pollution Intercurrent illness

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Diesel Exposure<br>1 hour exposure to dilute diesel exhaust at a concentration of 300 µg/m3 with intermittent exercise | Procedure: Forearm Vascular Study<br>* 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).<br>* Other names: BK;|
| Experimental: Air Exposure<br>1 hour exposure to filtered air during intermittent exercise | Procedure: Forearm Vascular Study<br>* 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).<br>* Other names: BK;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | 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 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma nitrite concentrations |  | During forearm study | 
| Plasma concentrations of t-PA and PAI |  | After infusion of bradykinin during forearm study | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Nitric Oxide, Nitric Oxide Synthase, Air Pollution, Endothelial Dysfunction, Diesel Exhaust