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

This study is not yet open for participant recruitment.
Verified August 2012 by University of Edinburgh
Sponsor:
Collaborators:
NHS Lothian
Umeå University
Information provided by (Responsible Party):
Jeremy Langrish, University of Edinburgh
ClinicalTrials.gov Identifier:
NCT00845169
First received: February 17, 2009
Last updated: August 3, 2012
Last verified: August 2012
  Purpose

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.


Condition Intervention
Endothelial Dysfunction
Procedure: Forearm vascular study

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Basic Science
Official Title: The Role of Nitric Oxide Synthase Isoforms in the Cardiovascular Effects of Air Pollution

Resource links provided by NLM:


Further study details as provided by University of Edinburgh:

Primary Outcome Measures:
  • 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. [ Time Frame: 2-4 hours after exposure ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Plasma nitrite concentration [ Time Frame: During forearm study ] [ Designated as safety issue: No ]

Estimated Enrollment: 16
Study Start Date: April 2012
Estimated Study Completion Date: June 2013
Estimated Primary Completion Date: June 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Diesel Exposure
1 hour exposure to diesel exhaust at 300 µg/m3 during intermittent exercise
Procedure: Forearm vascular study
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)
Other Names:
  • 1400W
  • SMTC
  • L-NMMA
  • Noreadrenaline
  • NorAd
Experimental: Air Exposure
1 hour exposure to filtered air during intermittent exercise
Procedure: Forearm vascular study
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)
Other Names:
  • 1400W
  • SMTC
  • L-NMMA
  • Noreadrenaline
  • NorAd

  Eligibility

Ages Eligible for Study:   18 Years to 40 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Healthy volunteers

Exclusion Criteria:

  • Regular medication use (except oral contraceptive pill)
  • Current smokers
  • Significant occupational exposure to air pollution
  • Intercurrent illness
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00845169

Contacts
Contact: Anders Blomberg, MD PhD +46 90 785 2234 anders.blomberg@lung.umu.se

Locations
Sweden
Umeå University Not yet recruiting
Umeå, Sweden
Principal Investigator: Anders Blomberg, MD PhD         
Sub-Investigator: Jeremy P Langrish, MB BCh MRCP         
Sub-Investigator: Nicholas L Mills, MB BCh MRCP         
Sub-Investigator: Magnus Lundbäck, MD         
Sub-Investigator: Stefan Barath, MD         
Sponsors and Collaborators
University of Edinburgh
NHS Lothian
Umeå University
Investigators
Principal Investigator: Anders Blomberg, MD PhD Umeå University
Principal Investigator: David E Newby, PhD FRCP University of Edinburgh
  More Information

No publications provided

Responsible Party: Jeremy Langrish, Clinical Lecturer and Specialty Registrar in Cardiology, University of Edinburgh
ClinicalTrials.gov Identifier: NCT00845169     History of Changes
Other Study ID Numbers: DNR 08-185M/2
Study First Received: February 17, 2009
Last Updated: August 3, 2012
Health Authority: Sweden: Regional Ethical Review Board

Keywords provided by University of Edinburgh:
Air Pollution
Nitric Oxide
Nitric Oxide Synthase
Diesel exhaust
endothelial dysfunction

Additional relevant MeSH terms:
Nitric Oxide
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Asthmatic Agents
Respiratory System Agents
Therapeutic Uses
Free Radical Scavengers
Antioxidants
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Endothelium-Dependent Relaxing Factors
Vasodilator Agents
Cardiovascular Agents
Protective Agents

ClinicalTrials.gov processed this record on April 16, 2014