title: Exposure to ultrafine carbon particles at levels below detectable pulmonary inflammation affects cardiovascular performance in spontaneously hypertensive rats.
abstract: BACKGROUND
  Exposure 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 mug.m-3), to assess whether compromised animals (SHR) exhibit a different response pattern compared to the previously studied healthy rats (WKY).
  
  
  METHODS
  Cardiophysiological 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).
  
  
  RESULTS
  Increased 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.
  
  
  CONCLUSIONS
  Our 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.
authors.affiliation: EPA-NHEERL, Research Triangle Park, NC 27709, USA. Kodavanti.Urmila@epamail.epa.gov.
authors.forename: Swapna
authors.initials: S
authors.lastname: Upadhyay
authors.forename: Tobias
authors.initials: T
authors.lastname: Stoeger
authors.forename: Volkar
authors.initials: V
authors.lastname: Harder
authors.forename: Ronald F
authors.initials: RF
authors.lastname: Thomas
authors.forename: Mette C
authors.initials: MC
authors.lastname: Schladweiler
authors.forename: Manuela
authors.initials: M
authors.lastname: Semmler-Behnke
authors.forename: Shinji
authors.initials: S
authors.lastname: Takenaka
authors.forename: Erwin
authors.initials: E
authors.lastname: Karg
authors.forename: Peter
authors.initials: P
authors.lastname: Reitmeir
authors.forename: Michael
authors.initials: M
authors.lastname: Bader
authors.forename: Andreas
authors.initials: A
authors.lastname: Stampfl
authors.forename: Urmila P
authors.initials: UP
authors.lastname: Kodavanti
authors.forename: Holger
authors.initials: H
authors.lastname: Schulz