title: Pulse pressure-dependent cerebrovascular eNOS regulation in mice.
abstract: Arterial blood pressure is oscillatory; whether pulse pressure (PP) regulates cerebral artery myogenic tone (MT) and endothelial function is currently unknown. To test the impact of PP on MT and dilation to flow (FMD) or to acetylcholine (Ach), isolated pressurized mouse posterior cerebral arteries were subjected to either static pressure (SP) or a physiological PP (amplitude: 30 mm Hg; frequency: 550 bpm). Under PP, MT was significantly higher than in SP conditions ( p < 0.05) and was not affected by eNOS inhibition. In contrast, under SP, eNOS inhibition increased ( p < 0.05) MT to levels observed under PP, suggesting that PP may inhibit eNOS. At a shear stress of 20 dyn/cm2, FMD was lower ( p < 0.05) under SP than PP. Under SP, eNOS-dependent [Formula: see text] production contributed to FMD, while under PP, eNOS-dependent NO was responsible for FMD, indicating that PP favours eNOS coupling. Differences in FMD between pressure conditions were abolished after NOX2 inhibition. In contrast to FMD, Ach-induced dilations were higher ( p < 0.05) under SP than PP. Reactive oxygen species scavenging reduced ( p < 0.05) Ach-dependent dilations under SP, but increased ( p < 0.05) them under PP; hence, under PP, Ach promotes ROS production and limits eNOS-derived NO activity. In conclusion, PP finely regulates eNOS, controlling cerebral artery reactivity.
authors.affiliation: 1 Faculty of Medicine, Department of Pharmacology, Université de Montréal, Montreal, Quebec, Canada.|2 Montreal Heart Institute Research Center, Montreal, Quebec, Canada.
authors.forename: Adeline
authors.initials: A
authors.lastname: Raignault
authors.affiliation: 1 Faculty of Medicine, Department of Pharmacology, Université de Montréal, Montreal, Quebec, Canada.|2 Montreal Heart Institute Research Center, Montreal, Quebec, Canada.
authors.forename: Virginie
authors.initials: V
authors.lastname: Bolduc
authors.affiliation: 2 Montreal Heart Institute Research Center, Montreal, Quebec, Canada.|3 Ecole Polytechnique de Montréal, Montreal, Quebec, Canada.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Lesage
authors.affiliation: 1 Faculty of Medicine, Department of Pharmacology, Université de Montréal, Montreal, Quebec, Canada.|2 Montreal Heart Institute Research Center, Montreal, Quebec, Canada.|4 Faculty of Medicine, Department of Surgery, Université de Montréal, Montreal, Quebec, Canada.
authors.forename: Eric
authors.initials: E
authors.lastname: Thorin
mesh_terms: D000818:Animals; D001794:Blood Pressure; D002531:Cerebellum / Q000098:blood supply*; D002536:Cerebral Arteries / Q000502:physiology*; D006339:Heart Rate; D006861:Hydrogen Peroxide / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009569:Nitric Oxide / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D014664:Vasodilation
chemical_list: D017382:Reactive Oxygen Species; D009569:Nitric Oxide; D006861:Hydrogen Peroxide; D052250:Nitric Oxide Synthase Type III; C496315:Nos3 protein, mouse
keywords: Hydrogen peroxide; NADPH oxidases; acetylcholine; myogenic tone; nitric oxide; shear stress
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