Vascular Function in Healthy Volunteers
Conditions
Keywords
Nitric oxide, Diesel exhaust, Air pollution, Cardiac output, Healthy volunteers
Brief summary
Exposure to combustion-derived fine particulate air pollution is associated with cardiovascular mortality and morbidity. In previous studies, exposure to diesel exhaust (a major constituent of urban particulate air pollution) has been shown to impair two important functions of the vascular endothelium: vascular vasomotor function and endogenous fibrinolysis. Our subsequent studies suggest this impairment of vascular function is mediated by a reduction in nitric oxide bioavailability. In this study we aim to investigate the cardiovascular responses to systemic nitric oxide synthase inhibition following exposure to dilute diesel exhaust.
Interventions
DRUGIntravenous infusion of L-NMMA and Nor-epinephrine
Intravenous infusion of 3mg/kg L-NMMA (L-NG-monomethyl arginine; NO synthase inhibitor) and nor-epinephrine at 50 ng/kg/min. Each infusion to run over 15 mins and separated by 45 min to allow return to baseline. Drugs infused in a randomised order. During the study, blood pressure will be measured invasively using an intra-arterial radial artery cannula, central arterial stiffness measured using peripheral arterial tonometry and cardiac output using thoracic bioimpedance.
Sponsors
NHS Lothian
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
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Healthy volunteers * Non smokers * No regular medication (except oral contraceptive) * No recent respiratory tract infection (within 6 weeks)
Exclusion criteria
* History of asthma or respiratory disease * Smoking history * Pregnancy (positive urinary pregnancy test)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Blood pressure response to NO inhibition | Blood pressure will be measured continuously through the vascular study using intra-arterial monitoring |
Secondary
| Measure | Time frame |
|---|---|
| Central arterial stiffness following NO inhibition | Measured at baseline, and every 5 minutes during the 2-hour vascular study |
| Cardiac output during NO inhibition | Measured at baseline, and every 5 minutes during the 2-hour vascular study |
| Heart rate response to systemic nitric oxide inhibition | Heart rate will be measured continuously throughout the study period using continous electrocardiography |
| Platelet activation and platelet-monocyte binding | Measured at baseline, and every 30 minutes during the 2-hour vascular study |
| Heart rate variability | Heart rate will be measured continuously throughout the study period using continous electrocardiography, and HRV subsequently determined for the whole study period and the 2-hour vascular study separately |
| Plasma nitrite (NO) concentrations | Measured at baseline, and every 15 minutes during the 2-hour vascular study |
Countries
Sweden
Outcome results
None listed