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

This study has been completed.
Sponsor:
Collaborator:
Umeå University
Information provided by:
University of Edinburgh
ClinicalTrials.gov Identifier:
NCT00845767
First received: February 17, 2009
Last updated: October 8, 2009
Last verified: October 2009
  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 (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 Cardiovascular Effects of Air Pollution: the Role of Nitric Oxide

Resource links provided by NLM:


Further study details as provided by University of Edinburgh:

Primary Outcome Measures:
  • Forearm blood flow as measured by venous occlusion plethysmography during infusion of NOS inhibitors and vasodilators [ Time Frame: 2-4 hours after exposure ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Plasma nitrite concentrations [ Time Frame: During forearm study ] [ Designated as safety issue: No ]
  • Plasma concentrations of t-PA and PAI [ Time Frame: After infusion of bradykinin during forearm study ] [ Designated as safety issue: No ]

Estimated Enrollment: 16
Study Start Date: April 2009
Study Completion Date: July 2009
Primary Completion Date: July 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Diesel Exposure
1 hour exposure to dilute diesel exhaust at a concentration of 300 µg/m3 with intermittent exercise
Procedure: 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).
Other Names:
  • ACh
  • SNP
  • BK
Experimental: Air Exposure
1 hour exposure to filtered air during intermittent exercise
Procedure: 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).
Other Names:
  • ACh
  • SNP
  • BK

  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:

  • Use of regular medication (except oral contraceptive pill)
  • Current smokers
  • Significant occupational exposure to air pollution
  • Intercurrent illness
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00845767

Locations
Sweden
Umeå University
Umeå, Sweden
Sponsors and Collaborators
University of Edinburgh
Umeå University
Investigators
Principal Investigator: Anders Blomberg, MD PhD Umeå University
Principal Investigator: David E Newby, PhD FRCP University of Edinburgh
  More Information

Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Dr Jeremy P Langrish, University of Edinburgh
ClinicalTrials.gov Identifier: NCT00845767     History of Changes
Other Study ID Numbers: DNR 08-185M/1
Study First Received: February 17, 2009
Last Updated: October 8, 2009
Health Authority: Sweden: Regional Ethical Review Board

Keywords provided by University of Edinburgh:
Nitric Oxide
Nitric Oxide Synthase
Air Pollution
Endothelial Dysfunction
Diesel Exhaust

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
Gasotransmitters
Protective Agents

ClinicalTrials.gov processed this record on October 16, 2014