The Role of Nitric Oxide Synthase Isoforms in the Cardiovascular Effects of Air Pollution

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 synthase isoforms (NO) in the adverse vascular responses observed following exposure to diesel exhaust.

Official Title
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The Role of Nitric Oxide Synthase Isoforms in the Cardiovascular Effects of Air Pollution

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: Regular medication use (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 diesel exhaust at 300 µg/m3 during intermittent exercise | Procedure: Forearm vascular study<br>* 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)<br>* Other names: NorAd;|
| Experimental: Air Exposure<br>1 hour exposure to filtered air during intermittent exercise | Procedure: Forearm vascular study<br>* 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)<br>* Other names: NorAd;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma nitrite concentration |  | During forearm study | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Air Pollution, Nitric Oxide, Nitric Oxide Synthase, Diesel exhaust, endothelial dysfunction