title: Vascular effects of ambient particulate matter instillation in spontaneous hypertensive rats.
abstract: Exposure to ambient particulate matter (PM) is associated with increased mortality and morbidity among those people with cardiovascular impairment. We have studied the effects of exposure to PM or lypopolysaccharide (LPS) on ex vivo vascular function of spontaneous hypertensive rats (SHR) at 4 and 24 h post-instillation. Receptor-dependent and -independent relaxation was studied by using acetylcholine (ACh) and sodium nitroprusside (SNP), respectively. We have used phenylephrine (Phe) and KCl for receptor-dependent and -independent contraction. The role of the endothelium was investigated using denuded aorta rings. Exposure to PM (EHC-93, 10 mg/kg) or LPS (350 EU/animal) caused maximal pulmonary inflammation at 24 h post-instillation. PM and LPS elicited a significant increase in receptor-dependent vasorelaxation of aorta compared to saline-instilled rats. The largest effect was seen with PM at 4 h post-instillation (EC50 ACh = 2.3 vs. 5 nM control), while at 24 h effects were much smaller (EC50 ACh = 5.6 vs. 5 nM control). SNP-induced vasorelaxation was increased only in EHC-93-treated rats (EC50 = 71.9 vs. 95.7 nM) at 4 h, and this response was higher than that observed at 24 h. Phe induced a dose-dependent vasoconstriction, but no difference was seen between treatments in the presence or absence of endothelium at 4 h. However, at 24 h after instillation of LPS, a right shift of contraction curve was seen (EC50 = 65.3 vs. 43.3 nM). No change was seen in receptor-independent vasoconstriction induced by KCl, except in the LPS group at 24 h. A direct relaxation was also observed upon in vitro exposure of aorta rings to PM, and model particles coated with metals. Blood metal analysis showed an increase of zinc and vanadium concentration at 1 and 4 h post-instillation. In conclusion, our data show that PM and LPS instillation has a transient effect on the vasorelaxation of rat aorta that is maximal at 4 h. On the other hand, pulmonary inflammation reaches a maximum at 24 h and coincides with impairment of vasorelaxation. Current data do not allow discriminating among the potential mechanisms, but suggest that both a direct effect of metals and inflammation play a role.
authors.affiliation: Particle Research, Institut fur Umweltmedizinische Forschung (IUF) at the University of Düsseldorf, NRW, 40225, Germany. Karim.bagate@uni-duesseldorf.de
authors.forename: Karim
authors.initials: K
authors.lastname: Bagate
authors.forename: James J
authors.initials: JJ
authors.lastname: Meiring
authors.forename: Miriam E
authors.initials: ME
authors.lastname: Gerlofs-Nijland
authors.forename: Renaud
authors.initials: R
authors.lastname: Vincent
authors.forename: Flemming R
authors.initials: FR
authors.lastname: Cassee
authors.forename: Paul J A
authors.initials: PJ
authors.lastname: Borm
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000393:Air Pollutants / Q000633:toxicity*; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000473:pathology; D001808:Blood Vessels / Q000187:drug effects / Q000473:pathology*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D006439:Hemodynamics / Q000187:drug effects*; D066298:In Vitro Techniques; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D008670:Metals / Q000493:pharmacokinetics; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D020556:Neutrophil Infiltration / Q000187:drug effects; D009599:Nitroprusside / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D014657:Vasculitis / Q000139:chemically induced / Q000473:pathology; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D000393:Air Pollutants; D008070:Lipopolysaccharides; D008670:Metals; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D009599:Nitroprusside; D010656:Phenylephrine; D000109:Acetylcholine