title: Pulmonary diesel particulate increases susceptibility to myocardial ischemia/reperfusion injury via activation of sensory TRPV1 and β1 adrenoreceptors.
abstract: BACKGROUND
  Clinical studies have now confirmed the link between short-term exposure to elevated levels of air pollution and increased cardiovascular mortality, but the mechanisms are complex and not completely elucidated. The present study was designed to investigate the hypothesis that activation of pulmonary sensory receptors and the sympathetic nervous system underlies the influence of pulmonary exposure to diesel exhaust particulate on blood pressure, and on the myocardial response to ischemia and reperfusion.
  
  
  RESULTS
  6 h after intratracheal instillation of diesel exhaust particulate (0.5 mg), myocardial ischemia and reperfusion was performed in anesthetised rats. Blood pressure, duration of ventricular arrhythmia, arrhythmia-associated death, tissue edema and reperfusion injury were all increased by diesel exhaust particulate exposure. Reperfusion injury was also increased in buffer perfused hearts isolated from rats instilled in vivo, excluding an effect dependent on continuous neurohumoral activation or systemic inflammatory mediators. Myocardial oxidant radical production, tissue apoptosis and necrosis were increased prior to ischemia, in the absence of recruited inflammatory cells. Intratracheal application of an antagonist of the vanilloid receptor TRPV1 (AMG 9810, 30 mg/kg) prevented enhancement of systolic blood pressure and arrhythmia in vivo, as well as basal and reperfusion-induced myocardial injury ex vivo. Systemic β1 adrenoreceptor antagonism with metoprolol (10 mg/kg) also blocked enhancement of myocardial oxidative stress and reperfusion injury.
  
  
  CONCLUSIONS
  Pulmonary diesel exhaust particulate increases blood pressure and has a profound adverse effect on the myocardium, resulting in tissue damage, but also increases vulnerability to ischemia-associated arrhythmia and reperfusion injury. These effects are mediated through activation of pulmonary TRPV1, the sympathetic nervous system and locally generated oxidative stress.
authors.forename: Sarah
authors.initials: S
authors.lastname: Robertson
authors.forename: Ashleigh L
authors.initials: AL
authors.lastname: Thomson
authors.forename: Rod
authors.initials: R
authors.lastname: Carter
authors.forename: Holly R
authors.initials: HR
authors.lastname: Stott
authors.forename: Catherine A
authors.initials: CA
authors.lastname: Shaw
authors.forename: Patrick W F
authors.initials: PW
authors.lastname: Hadoke
authors.forename: David E
authors.initials: DE
authors.lastname: Newby
authors.forename: Mark R
authors.initials: MR
authors.lastname: Miller
authors.affiliation: BHF/ University Centre for Cardiovascular Science, Queens Medical Research Institute, University of Edinburgh, Edinburgh, Scotland, UK. gillian.gray@ed.ac.uk.
authors.forename: Gillian A
authors.initials: GA
authors.lastname: Gray
mesh_terms: D000393:Air Pollutants / Q000633:toxicity*; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000139:chemically induced / Q000503:physiopathology; D001794:Blood Pressure / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D007278:Injections, Spinal; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000401:mortality / Q000473:pathology* / Q000503:physiopathology; D009206:Myocardium / Q000473:pathology; D020556:Neutrophil Infiltration / Q000187:drug effects; D052638:Particulate Matter / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D018342:Receptors, Adrenergic, beta-1 / Q000187:drug effects*; D011984:Sensory Receptor Cells / Q000187:drug effects; D050916:TRPV Cation Channels / Q000187:drug effects*; D001335:Vehicle Emissions / Q000633:toxicity*
chemical_list: D000393:Air Pollutants; D052638:Particulate Matter; D018342:Receptors, Adrenergic, beta-1; D050916:TRPV Cation Channels; C493922:Trpv1 protein, rat; D001335:Vehicle Emissions