Blood Pressure Response to Controlled Diesel Exhaust Inhalation in Human Subjects Is Modified by Functional Variation in TRPV1

Details

• Personal Author:
  Cosselman K ; Jansen K ; Kaufman JD ; Krishnan RM ; Larson TV ; Oron AP ; Peretz A
• Description:
  Background: Exposure to traffic-related air pollution is associated with increased risk of cardiovascular disease and mortality. Diesel exhaust (DE) inhalation is a model exposure, and we hypothesize that pollutants trigger acute cardiovascular events via neurogenic processes. We evaluated blood pressure (BP) response to DE and whether the effect was modified by genotype for the transient receptor potential receptor, vanilloid type 1 (TRPV1), a non-selective cation channel expressed in the lung and activated by noxious chemical stimuli. The t allele for the TRPV1 single nucleotide polymorphism rs8065080 at position 585 results in Ile substituting for Val, and has been associated with reduced nociception. Methods: Forty-seven non-smokers, age 18-49 with no prior cardiovascular or pulmonary disease, underwent controlled exposures to each condition [DE at 200 u g/m3 PM2.5 and filtered air (FA)] for 120 minutes in a crossover experiment. Exposures were double-blind, randomized to order, and separated by at least 2 weeks. We measured BP pre-exposure, at 5 time points during exposure, and 3, 5, 7 and 24 hours from exposure start. We analyzed pressure change (from pre-exposure values) for each exposure to determine the difference between DE and FA. Results: Compared with FA, systolic blood pressure (SBP) increased at all time points measured during and after DE exposure (p=0.004); mean effect peaked 30 to 90 minutes after exposure began (3.9 mmHg, p=0.01). No effects were observed for heart rate or diastolic BP. SBP response varied by TRPV1 Ile585Val genotype, with t/t subjects showing the lowest SBP response to DE (see Figure). Conclusion: DE exposure was associated with a rapid increase in SBP, with a reduced response in subjects with the Ile-Ile variation of TRPV1. This suggests that TRPV1 activation by a component of DE may be a key step explaining observed vascular effects of air pollution, perhaps by initiating autonomic signaling or neurogenic inflammation. [Description provided by NIOSH]
• Subjects:
  Air Pollution Cardiovascular Diseases Cardiovascular System Epidemiology Genetics Occupational Exposure Occupational Health Particulate Matter Risk Assessment Risk Factors Safety

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• Keywords:
  Air Pollution Author Keywords: Air Pollution Autonomic Nervous System Blood Pressure Cardiovascular Disease Chronic Exposure Diesel Exhaust Health Effects Particulates Risk Factors
• ISSN:
  0009-7322
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Abstract or Summary
• Place as Subject:
  OSHA Region 10 ; Washington
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  124
• NIOSHTIC Number:
  nn:20054898
• Citation:
  Circulation 2011 Nov; 124(Suppl 21):A17098
• Federal Fiscal Year:
  2012
• Performing Organization:
  University of Washington
• Peer Reviewed:
  True
• Start Date:
  20050701
• Source Full Name:
  Circulation
• Supplement:
  Suppl 21
• End Date:
  20250630
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:6f22721cb8dc79f0d29b3e99b9aac0a80bd1ae225e611a1807c3a068ae950df0c2ee82e12baf8209c2485c45effd0037885d2738c68897de3a8d22e494d71a9e
• Download URL:
  https://stacks.cdc.gov/view/cdc/217311/cdc_217311_DS1.pdf
• File Type:
  [PDF - 71.09 KB ]