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

NCT00845169 | Completed

• 1 other identifier: DNR 08-185M/2
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

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

Conditions

Endothelial Dysfunction

Keywords

Air Pollution; Nitric Oxide; Nitric Oxide Synthase; Diesel exhaust; endothelial dysfunction

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• Plasma nitrite concentration

  During forearm study

Study Arms (2)

Diesel Exposure

EXPERIMENTAL

1 hour exposure to diesel exhaust at 300 µg/m3 during intermittent exercise

Procedure: Forearm vascular study

Air Exposure

EXPERIMENTAL

1 hour exposure to filtered air during intermittent exercise

Procedure: Forearm vascular study

Interventions

Forearm vascular study PROCEDURE

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)

Also known as: 1400W, SMTC, L-NMMA, Noreadrenaline, NorAd

Air Exposure; Diesel Exposure

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy volunteers

You may not qualify if:

• Regular medication use (except oral contraceptive pill)
• Current smokers
• Significant occupational exposure to air pollution
• Intercurrent illness

Sponsors & Collaborators

• University of Edinburgh: lead
• NHS Lothian: collaborator
• Umeå University: collaborator

Study Sites (1)

Umeå University

Umeå, Sweden

Location

MeSH Terms

Interventions

omega-N-Methylarginine

Intervention Hierarchy (Ancestors)

Arginine; Amino Acids, Basic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Diamino; Amino Acids, Essential

Study Officials

• Anders Blomberg, MD PhD

  Umeå University

  PRINCIPAL INVESTIGATOR

• David E Newby, PhD FRCP

  University of Edinburgh

  PRINCIPAL INVESTIGATOR

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: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Lecturer and Specialty Registrar in Cardiology

Study Record Dates

• First Submitted: February 17, 2009
• First Posted: February 18, 2009
• Study Start: April 1, 2012
• Primary Completion: June 1, 2013
• Study Completion: June 1, 2013
• Last Updated: December 2, 2014

Record last verified: 2014-12

Locations

SE (1)