The Effects of Diesel Exhaust Inhalation on Vascular Function - the Role of Endothelin

NCT00745693 | Completed

• 1 other identifier: Res08/A116
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to identify the role of endothelin 1 (a natural vasoconstrictor) in the adverse vascular effects demonstrated after exposure to air pollution

Conditions

Coronary Disease

Keywords

Endothelin; Air pollution; Diesel exhaust; Vascular function; exposure

Outcome Measures

Primary Outcomes (1)

• Change in forearm blood flow following infusion of endothelin-1 or the endothelin receptor antagonists BQ-123 & BQ-788

  2 hours after exposure

Secondary Outcomes (3)

• 24 hour mean blood pressure (ambulatory monitoring)

  24 hours following the exposure

• Systemic endothelin-1 and big endothelin-1 concentrations

  At baseline, and immediately, 1, 2, 3, 4, 6 and 24 hours after exposure

• Changes in arterial stiffness (pulse-wave velocity)

  During and for the 1 hour after the exposure

Study Arms (4)

1

EXPERIMENTAL

1 hour exposure to filtered air, followed by forearm venous occlusion plethysmography at 2 hours after the exposure and infusion of endothelin-1 (5pmol/min)

Drug: Endothelin-1

2

EXPERIMENTAL

1 hour exposure to filtered air, followed by forearm venous occlusion plethysmography at 2 hours after the exposure and infusion of endothelin receptor antagonists BQ-123 and BQ-788

Drug: BQ-123 and BQ-788

3

EXPERIMENTAL

1 hour exposure to dilute diesel exhaust (300mcg/m3), followed by forearm venous occlusion plethysmography at 2 hours after the exposure and infusion of endothelin-1 (5pmol/min)

Drug: Endothelin-1

4

EXPERIMENTAL

1 hour exposure to dilute diesel exhaust (300mcg/m3), followed by forearm venous occlusion plethysmography at 2 hours after the exposure and infusion of endothelin receptor antagonists BQ-123 and BQ-788

Drug: BQ-123 and BQ-788

Interventions

Endothelin-1 DRUG

Intra-arterial infusion of Endothelin-1 at 5pmol/min for 1 hour during venous occlusion plethysmography

Also known as: ET-1, American Peptides - 88-1-10 (ET-1)

1; 3

BQ-123 and BQ-788 DRUG

1 hour intra-arterial infusion of BQ-123 at 10nmol/min followed by co-infusion of BQ-788 at 1nmol/min for a further hour during forearm venous occlusion plethysmography

Also known as: American Peptides - 88-2-10 (BQ-123), American Peptides - 88-2-55 (BQ-788)

2; 4

Eligibility Criteria

• Age: 18 Years - 35 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy male volunteers

You may not qualify if:

• Use of regular medication
• Cigarette smoking
• Significant occupational exposure to air pollution
• Intercurrent illness

Sponsors & Collaborators

• University of Edinburgh: lead
• Umeå University: collaborator

Study Sites (1)

Umeå University

Umeå, Västerbottens, SE-901 87, Sweden

Location

Related Publications (6)

• 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.

  PMID: 16365212 BACKGROUND

• Tornqvist H, Mills NL, Gonzalez M, Miller MR, Robinson SD, Megson IL, Macnee W, Donaldson K, Soderberg S, Newby DE, Sandstrom T, Blomberg A. Persistent endothelial dysfunction in humans after diesel exhaust inhalation. Am J Respir Crit Care Med. 2007 Aug 15;176(4):395-400. doi: 10.1164/rccm.200606-872OC. Epub 2007 Apr 19.

  PMID: 17446340 BACKGROUND

• Calderon-Garciduenas L, Vincent R, Mora-Tiscareno A, Franco-Lira M, Henriquez-Roldan C, Barragan-Mejia G, Garrido-Garcia L, Camacho-Reyes L, Valencia-Salazar G, Paredes R, Romero L, Osnaya H, Villarreal-Calderon R, Torres-Jardon R, Hazucha MJ, Reed W. Elevated plasma endothelin-1 and pulmonary arterial pressure in children exposed to air pollution. Environ Health Perspect. 2007 Aug;115(8):1248-53. doi: 10.1289/ehp.9641.

  PMID: 17687455 BACKGROUND

• Peretz A, Sullivan JH, Leotta DF, Trenga CA, Sands FN, Allen J, Carlsten C, Wilkinson CW, Gill EA, Kaufman JD. Diesel exhaust inhalation elicits acute vasoconstriction in vivo. Environ Health Perspect. 2008 Jul;116(7):937-42. doi: 10.1289/ehp.11027.

  PMID: 18629317 BACKGROUND

• Vincent R, Kumarathasan P, Goegan P, Bjarnason SG, Guenette J, Berube D, Adamson IY, Desjardins S, Burnett RT, Miller FJ, Battistini B. Inhalation toxicology of urban ambient particulate matter: acute cardiovascular effects in rats. Res Rep Health Eff Inst. 2001 Oct;(104):5-54; discussion 55-62.

  PMID: 11833973 BACKGROUND

• Langrish JP, Lundback M, Mills NL, Johnston NR, Webb DJ, Sandstrom T, Blomberg A, Newby DE. Contribution of endothelin 1 to the vascular effects of diesel exhaust inhalation in humans. Hypertension. 2009 Oct;54(4):910-5. doi: 10.1161/HYPERTENSIONAHA.109.135947. Epub 2009 Aug 17.

  PMID: 19687345 DERIVED

MeSH Terms

Conditions

Coronary Disease

Interventions

Endothelin-1; cyclo(Trp-Asp-Pro-Val-Leu); BQ 788

Condition Hierarchy (Ancestors)

Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases

Intervention Hierarchy (Ancestors)

Endothelins; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Study Officials

• Jeremy P Langrish, MB BCh MRCP

  University of Edinburgh

  PRINCIPAL INVESTIGATOR

• Anders Blomberg, MD

  Umeå University

  STUDY DIRECTOR

• Thomas Sandström, MD

  Umeå University

  STUDY DIRECTOR

• David E Newby, MD FRCP

  University of Edinburgh

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 2, 2008
• First Posted: September 3, 2008
• Study Start: March 1, 2008
• Primary Completion: May 1, 2008
• Study Completion: May 1, 2008
• Last Updated: May 17, 2024

Record last verified: 2008-09

Locations

SE (1)