Abstract
BackgroundExposure to particulate matter is a risk factor for cardiopulmonary disease but the underlying molecular mechanisms remain poorly understood. In the present study we sought to investigate the cardiopulmonary responses on spontaneously hypertensive rats (SHRs) following inhalation of UfCPs (24 h, 172 μg·m-3), to assess whether compromised animals (SHR) exhibit a different response pattern compared to the previously studied healthy rats (WKY).MethodsCardiophysiological response in SHRs was analyzed using radiotelemetry. Blood pressure (BP) and its biomarkers plasma renin-angiotensin system were also assessed. Lung and cardiac mRNA expressions for markers of oxidative stress (hemeoxygenase-1), blood coagulation (tissue factor, plasminogen activator inhibitor-1), and endothelial function (endothelin-1, and endothelin receptors A and B) were analyzed following UfCPs exposure in SHRs. UfCPs-mediated inflammatory responses were assessed from broncho-alveolar-lavage fluid (BALF).ResultsIncreased BP and heart rate (HR) by about 5% with a lag of 1–3 days were detected in UfCPs exposed SHRs. Inflammatory markers of BALF, lung (pulmonary) and blood (systemic) were not affected. However, mRNA expression of hemeoxygenase-1, endothelin-1, endothelin receptors A and B, tissue factor, and plasminogen activator inhibitor showed a significant induction (~2.5-fold; p < 0.05) with endothelin 1 being the maximally induced factor (6-fold; p < 0.05) on the third recovery day in the lungs of UfCPs exposed SHRs; while all of these factors – except hemeoxygenase-1 – were not affected in cardiac tissues. Strikingly, the UfCPs-mediated altered BP is paralleled by the induction of renin-angiotensin system in plasma.ConclusionOur finding shows that UfCPs exposure at levels which does not induce detectable pulmonary neutrophilic inflammation, triggers distinct effects in the lung and also at the systemic level in compromised SHRs. These effects are characterized by increased activity of plasma renin-angiotensin system and circulating white blood cells together with moderate increases in the BP, HR and decreases in heart rate variability. This systemic effect is associated with pulmonary, but not cardiac, mRNA induction of biomarkers reflective of oxidative stress; activation of vasoconstriction, stimulation of blood coagulation factors, and inhibition of fibrinolysis. Thus, UfCPs may cause cardiovascular and pulmonary impairment, in the absence of detectable pulmonary inflammation, in individuals suffering from preexisting cardiovascular diseases.
Highlights
Exposure to particulate matter is a risk factor for cardiopulmonary disease but the underlying molecular mechanisms remain poorly understood
Considering this observation we hypothesize that spontaneously hypertensive rats (SHR) are at higher risk and more susceptible or vulnerable to cardiovascular impairments following exposure to UFCPs compared to healthy Wistar Kyoto (WKY) as no pulmonary injury or coagulative changes were observed in WKY exposed to ultrafine carbon particles (UfCPs) [9]
We have shown that inhalation of UfCPs at concentrations reflecting peak ambient exposures results in a moderate increase in heart rate (HR) and Blood pressure (BP) in SHRs with a lag of 1–3 days which is paralleled by the induction of reninangiotensin system in plasma, potentially being due to an activation of the local pulmonary rennin-angiotensin system
Summary
Exposure to particulate matter is a risk factor for cardiopulmonary disease but the underlying molecular mechanisms remain poorly understood. Exposure to airborne UFPs may cause a low-grade pulmonary inflammation by inducing the generation of reactive oxygen species and pro-inflammatory cytokines like TNFα, IL-1, IL-6 [11]. This could be associated with increased plasma viscosity [12]; blood coagulability [13], vascular and endothelial dysfunction [14,15]. There are evidences that UFPs deposited in the lung gain access to the systemic circulation and translocate into extra-pulmonary organs, such as liver, heart, and brain [16,17] This may disturb the blood coagulation balance by activating circulating platelets [18,19] but may induce dysfunction in secondary target organs [20,21]
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