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

NCT ID: NCT00845767

Last Updated: 2009-10-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 16 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-04-30
• Study Completion Date: 2009-07-31

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

Conditions

Endothelial Dysfunction

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: TRIPLE

Study Groups

Diesel Exposure

1 hour exposure to dilute diesel exhaust at a concentration of 300 µg/m3 with intermittent exercise

Group Type: EXPERIMENTAL

Forearm Vascular Study

Intervention Type: PROCEDURE

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).

Air Exposure

1 hour exposure to filtered air during intermittent exercise

Group Type: EXPERIMENTAL

Forearm Vascular Study

Intervention Type: PROCEDURE

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).

Interventions

Forearm Vascular Study

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).

Intervention Type: PROCEDURE

Other Intervention Names

ACh; SNP; BK

Eligibility Criteria

Inclusion Criteria

• Healthy volunteers

Exclusion Criteria

• Use of regular medication (except oral contraceptive pill)
• Current smokers
• Significant occupational exposure to air pollution
• Intercurrent illness

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 40 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Umeå University

OTHER

Sponsor Role: collaborator

University of Edinburgh

OTHER

Sponsor Role: lead

Responsible Party

University of Edinburgh

Principal Investigators

Anders Blomberg, MD PhD

Role: PRINCIPAL_INVESTIGATOR

Umeå University

David E Newby, PhD FRCP

Role: PRINCIPAL_INVESTIGATOR

University of Edinburgh

Locations

Umeå University

Umeå, , Sweden

Countries

Sweden

References

Mills NL, Tornqvist H, Robinson SD, Gonzalez M, Darnley K, MacNee W, Boon NA, Donaldson K, Blomberg A, Sandstrom T, Newby DE. Diesel exhaust inhalation causes vascular dysfunction and impaired endogenous fibrinolysis. Circulation. 2005 Dec 20;112(25):3930-6. doi: 10.1161/CIRCULATIONAHA.105.588962.

Reference Type: BACKGROUND

PMID: 16365212 (View on PubMed)

Langrish JP, Unosson J, Bosson J, Barath S, Muala A, Blackwell S, Soderberg S, Pourazar J, Megson IL, Treweeke A, Sandstrom T, Newby DE, Blomberg A, Mills NL. Altered nitric oxide bioavailability contributes to diesel exhaust inhalation-induced cardiovascular dysfunction in man. J Am Heart Assoc. 2013 Feb 19;2(1):e004309. doi: 10.1161/JAHA.112.004309.

Reference Type: DERIVED

PMID: 23525434 (View on PubMed)

Other Identifiers

DNR 08-185M/1

Identifier Type: -

Identifier Source: org_study_id