Diesel Exhaust Inhalation, Systemic Nitric Oxide Inhibition and Cardiac Output

Condition(s) targeted: Vascular Function in Healthy Volunteers

Intervention: Intravenous infusion of L-NMMA and Nor-epinephrine (Drug)

Phase: N/A

Status: Completed

Sponsored by: University of Edinburgh

Official(s) and/or principal investigator(s):
Jeremy P Langrish, MB BCh MRCP, Principal Investigator, Affiliation: University of Edinburgh

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.

Official title: Diesel Exhaust Inhalation, Systemic Nitric Oxide Inhibition and Cardiac Output

Study design: Allocation: Randomized, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Basic Science

Primary outcome: Blood pressure response to NO inhibition

Secondary outcome:

Heart rate response to systemic nitric oxide inhibition

Central arterial stiffness following NO inhibition

Cardiac output during NO inhibition

Plasma nitrite (NO) concentrations

Platelet activation and platelet-monocyte binding

Heart rate variability

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

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)

University Hospital Umeå, Umeå, Sweden

Starting date: March 2010
Last updated: December 15, 2011