Acute effects of fine particles on cardiovascular system: differences between the spontaneously hypertensive rats and wistar kyoto rats

Toxicol Lett. 2010 Mar 1;193(1):50-60. doi: 10.1016/j.toxlet.2009.12.002. Epub 2009 Dec 16.

Abstract

The study is to explore the potential mechanisms linking fine particles and cardiovascular toxicity. Spontaneous hypertensive rats (SHR) and age-matched wistar kyoto (WKY) rats were exposed by intratracheal instillation to fine particles with the doses of 0.0, 1.6, 8.0 and 40.0mg/kg b.w., respectively. The exposure was conducted once a day, for three continuous days. Twenty-four hours after the last exposure, the rats were killed and the levels of high sensitive C-reactive proteins (hsCRPs), nitrous oxide (NO), D-dimer and endothelin-1 (ET-1) were measured in blood. Reverse transcriptase polymerase chain reaction (RT-PCR) assay assessed the expression of interleukin-1 beta (IL-1beta), intercellular adhesion molecule-1 (ICAM-1), ET-1, Bax and Bcl-2 in left ventricle of rats. Meanwhile, cardiac histological lesions were assessed. The expression transforming growth factor-beta 1 (TGF-beta(1)) in left ventricle was measured by immunohistochemical staining. The results showed that the levels of hsCRP, D-dimer, ET-1 and the expression of IL-1beta, ICAM-1, ET-1, Bax and TGF-beta(1) increased in a dose-dependent manner, but NO and Bcl-2 decreased. Cardiac histology demonstrated exacerbated cardiac lesions in SHR when compared to WKY rats. Meanwhile, at the same dose exposed, the levels of hsCRP, d-dimer, ET-1 and the expression of IL-1beta, ICAM-1, ET-1, Bax and TGF-beta(1) were higher in SHR than those in WKY rats. The results indicated that ambient fine particles which entered into lungs could influence the cardiovascular system. When exposed to fine particles, SHR exhibited more severe cardiovascular injury in comparison to WKY rats. The results indicated that the inflammation, endothelial dysfunction, coagulation disorders and imbalance of apoptosis/anti-apoptosis might be the mechanisms of cardiovascular injury induced by fine particles. Different response between SHR and WKY rats after exposed to fine particles indicated that SHR was more susceptible than WKY rats to acute cardiac impairments from fine particle exposure.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood Cell Count
  • Blood Coagulation Factors / metabolism
  • C-Reactive Protein / analysis
  • C-Reactive Protein / metabolism
  • Cardiovascular System / drug effects*
  • Cytokines / biosynthesis
  • Endothelium, Vascular / drug effects
  • Immunohistochemistry
  • Inflammation / chemically induced
  • Inflammation / pathology
  • Inflammation Mediators / metabolism
  • Nanoparticles / toxicity*
  • Particle Size
  • RNA, Messenger / biosynthesis
  • Rats
  • Rats, Inbred SHR
  • Rats, Inbred WKY
  • Reverse Transcriptase Polymerase Chain Reaction
  • Species Specificity
  • Transforming Growth Factor beta1 / biosynthesis

Substances

  • Blood Coagulation Factors
  • Cytokines
  • Inflammation Mediators
  • RNA, Messenger
  • Transforming Growth Factor beta1
  • C-Reactive Protein