Diesel exhaust particulate induces pulmonary and systemic inflammation in rats without impairing endothelial function ex vivo or in vivo.

Abstract

BACKGROUND:

Inhalation of diesel exhaust impairs vascular function in man, by a mechanism that has yet to be fully established. We hypothesised that pulmonary exposure to diesel exhaust particles (DEP) would cause endothelial dysfunction in rats as a consequence of pulmonary and systemic inflammation.

METHODS:

Wistar rats were exposed to DEP (0.5 mg) or saline vehicle by intratracheal instillation and hind-limb blood flow, blood pressure and heart rate were monitored in situ 6 or 24 h after exposure. Vascular function was tested by administration of the endothelium-dependent vasodilator acetylcholine (ACh) and the endothelium-independent vasodilator sodium nitroprusside (SNP) in vivo and ex vivo in isolated rings of thoracic aorta, femoral and mesenteric artery from DEP exposed rats. Bronchoalveolar lavage fluid (BALF) and blood plasma were collected to assess pulmonary (cell differentials, protein levels & interleukin-6 (IL-6)) and systemic (IL-6), tumour necrosis factor alpha (TNFα) and C-reactive protein (CRP)) inflammation, respectively.

RESULTS:

DEP instillation increased cell counts, total protein and IL-6 in BALF 6 h after exposure, while levels of IL-6 and TNFα were only raised in blood 24 h after DEP exposure. DEP had no effect on the increased hind-limb blood flow induced by ACh in vivo at 6 or 24 h. However, responses to SNP were impaired at both time points. In contrast, ex vivo responses to ACh and SNP were unaltered in arteries isolated from rats exposed to DEP.

CONCLUSIONS:

Exposure of rats to DEP induces both pulmonary and systemic inflammation, but does not modify endothelium-dependent vasodilatation. Other mechanisms in vivo limit dilator responses to SNP and these require further investigation.

• Authors: Sarah Robertson, Gillian A Gray, Rodger Duffin, Steven G McLean, Catherine A Shaw, Patrick W F Hadoke, David E Newby, Mark R Miller
• Journal: Particle and fibre toxicology (Part Fibre Toxicol) Vol. 9 Pg. 9 (Apr 05 2012) ISSN: 1743-8977 [Electronic] England
• PMID: 22480168 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Endothelium-Dependent Relaxing Factors
• Interleukin-6
• Particulate Matter
• Tumor Necrosis Factor-alpha
• Vehicle Emissions
• C-Reactive Protein

Topics

• Animals
• Aorta, Thoracic (drug effects)
• Blood Cell Count
• Blood Platelets (cytology, drug effects)
• Blood Pressure (drug effects)
• Bronchoalveolar Lavage Fluid (chemistry, cytology, immunology)
• C-Reactive Protein (analysis)
• Cell Differentiation (drug effects)
• Endothelium, Vascular (drug effects)
• Endothelium-Dependent Relaxing Factors (pharmacology)
• Erythrocytes (cytology, drug effects)
• Femoral Artery (drug effects)
• Heart Rate (drug effects)
• In Vitro Techniques
• Interleukin-6 (analysis)
• Leukocytes (cytology, drug effects)
• Male
• Mesenteric Arteries (drug effects)
• Particulate Matter (analysis, toxicity)
• Pneumonia (blood, chemically induced, physiopathology)
• Rats
• Rats, Wistar
• Tumor Necrosis Factor-alpha (analysis)
• Vasodilation (drug effects)
• Vehicle Emissions (analysis, toxicity)