Montelukast prevents vascular endothelial dysfunction from internal combustion exhaust inhalation during exercise.
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.
Rundell
Kenneth W
KW
Human Physiology Laboratory, Marywood University, Scranton, Pennsylvania 18509, USA. rundell@marywood.edu
Steigerwald
Michelle D
MD
Fisk
Michelle Z
MZ
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
D000085:Acetates; D000393:Air Pollutants; D003521:Cyclopropanes; D020024:Leukotriene Antagonists; D011804:Quinolines; D013440:Sulfides; D001335:Vehicle Emissions; C093875:montelukast