title: Montelukast prevents vascular endothelial dysfunction from internal combustion exhaust inhalation during exercise.
abstract: Associations between high particulate matter (PM) pollution and increased morbidity and mortality from coronary heart disease have been identified. This study assessed leukotriene (LT) participation in PM-induced vascular endothelial dysfunction. Ten healthy males exercised 4 times for 30 min in both high PM (550,286 +/- 42,004 particles x cm(-3)) and low PM (4571 +/- 1922 particles x cm(-3)) after ingesting placebo (PL) or 10 mg montelukast (MK; half-life 3-6 h), a leukotriene receptor antagonist. Brachial artery flow-mediated dilation (FMD) was measured pre- and 30 min, 4 h, 24 h post-exercise. No basal brachial artery vascoconstriction was evident from high PM exercise. High PM blunted FMD, whereas high PM MK, low PM PL, and low PM MK demonstrated normal FMD (p < .003). Change in FMD (pre- to post-exercise) for high PM PL was different than for high PM MK, low PM PL, and low PM MK at 30 min post-exercise (p < .007). At 4 h, high PM MK FMD blunting increased (p = .1). At 24 h, high PM FMD blunting persisted (p < .05); no difference was observed between high PM PL or MK treatment, but was different that low PM PL/MK treatments (p < .05). MK blocked high PM post-exercise FMD blunting and maintained normal response, suggesting that leukotrienes are involved in PM-initiated vascular endothelial dysfunction.
authors.affiliation: Human Physiology Laboratory, Marywood University, Scranton, Pennsylvania 18509, USA. rundell@marywood.edu
authors.forename: Kenneth W
authors.initials: KW
authors.lastname: Rundell
authors.forename: Michelle D
authors.initials: MD
authors.lastname: Steigerwald
authors.forename: Michelle Z
authors.initials: MZ
authors.lastname: Fisk
mesh_terms: D000085:Acetates / Q000494:pharmacology*; D000393:Air Pollutants / Q000633:toxicity*; D001916:Brachial Artery / Q000187:drug effects / Q000503:physiopathology; D003521:Cyclopropanes; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005080:Exercise Test; D006801:Humans; D020024:Leukotriene Antagonists / Q000494:pharmacology*; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D010101:Oxygen Consumption; D011804:Quinolines / Q000494:pharmacology*; D012039:Regional Blood Flow / Q000187:drug effects; D013440:Sulfides; D014661:Vasoconstriction / Q000187:drug effects*; D014664:Vasodilation / Q000187:drug effects*; D001335:Vehicle Emissions / Q000633:toxicity*; D055815:Young Adult
chemical_list: D000085:Acetates; D000393:Air Pollutants; D003521:Cyclopropanes; D020024:Leukotriene Antagonists; D011804:Quinolines; D013440:Sulfides; D001335:Vehicle Emissions; C093875:montelukast