title: Carbon monoxide pollution impairs myocardial perfusion reserve: implication of coronary endothelial dysfunction.
abstract: Chronic exposure to simulated urban CO pollution is reported to be associated with cardiac dysfunction. Despite the potential implication of myocardial perfusion alteration in the pathophysiology of CO pollution, the underlying mechanisms remain today still unknown. Therefore, the aim of this work was to evaluate the effects of prolonged exposure to simulated urban CO pollution on the regulation of myocardial perfusion. Cardiac hemodynamics and myocardial perfusion were assessed under basal conditions and during the infusion of a β-Adrenergic agonist. The effects of CO exposure on capillary density, coronary endothelium-dependent vasodilatation, eNOS expression and eNOS uncoupling were also evaluated. Our main results were that prolonged CO exposure was associated with a blunted myocardial perfusion response to a physiological stress responsible for an altered contractile reserve. The impairment of myocardial perfusion reserve was not accounted for a reduced capillary density but rather by an alteration in coronary endothelium-dependent vasorelaxation (-45% of maximal relaxation to ACh). In addition, though chronic CO exposure did not change eNOS expression, it significantly increased eNOS uncoupling. Therefore, the present work underlines the fact that chronic CO exposure, at levels found in urban air pollution, is associated with reduced myocardial perfusion reserve. This phenomenon is explained at the coronary-vessel level by deleterious effects of CO exposure on the endothelium NO-dependent vasorelaxation via eNOS uncoupling.
authors.affiliation: Avignon University, France.
authors.forename: G
authors.initials: G
authors.lastname: Meyer
authors.forename: J
authors.initials: J
authors.lastname: Boissiere
authors.forename: S
authors.initials: S
authors.lastname: Tanguy
authors.forename: C
authors.initials: C
authors.lastname: Rugale
authors.forename: S
authors.initials: S
authors.lastname: Gayrard
authors.forename: B
authors.initials: B
authors.lastname: Jover
authors.forename: P
authors.initials: P
authors.lastname: Obert
authors.forename: C
authors.initials: C
authors.lastname: Reboul
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000393:Air Pollutants / Q000633:toxicity*; D000818:Animals; D002196:Capillaries / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D002248:Carbon Monoxide / Q000633:toxicity*; D003331:Coronary Vessels / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000503:physiopathology; D053805:Fractional Flow Reserve, Myocardial / Q000187:drug effects / Q000502:physiology; D006321:Heart / Q000187:drug effects*; D006439:Hemodynamics / Q000187:drug effects; D019570:Inhalation Exposure; D008297:Male; D009206:Myocardium / Q000473:pathology; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D009599:Nitroprusside / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology
chemical_list: D000393:Air Pollutants; D009599:Nitroprusside; D002248:Carbon Monoxide; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; D000109:Acetylcholine