title: Losartan abolishes oxidative stress induced by intermittent hypoxia in humans.
abstract: The aim of this study was to assess the role of the type 1 angiotensin II (AT(1)) receptor in the increase of oxidative stress and NO metabolism during a single 6 h exposure to intermittent hypoxia (IH). Nine healthy young men were exposed, while awake, to sham IH, IH with placebo medication, and IH with the AT(1) receptor antagonist, losartan, using a double-blind, placebo-controlled, randomized, crossover study design. In addition to blood pressure, oxidative stress, peroxynitrite activity, uric acid, global antioxidant status and the end-products of NO (NOx) metabolism were measured in plasma before and after 6 h of IH. Oxidative stress and peroxynitrite activity increased and NOx decreased during IH with placebo. In contrast, neither sham IH nor IH with losartan affected these parameters. With respect to each condition, blood pressure had the same profile as oxidative stress. These results demonstrate that blockade of AT(1) receptors prevented the increase in oxidative stress and peroxynitrite activity and the decrease in NO metabolism induced by IH. Finally, this study suggests that the renin-angiotensin system may participate in the overproduction of reactive oxygen species associated with IH by upregulation of the actions of angiotensin II.
authors.affiliation: Department of Physiology and Pharmacology, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Vincent
authors.initials: V
authors.lastname: Pialoux
authors.forename: Glen E
authors.initials: GE
authors.lastname: Foster
authors.forename: Sofia B
authors.initials: SB
authors.lastname: Ahmed
authors.forename: Andrew E
authors.initials: AE
authors.lastname: Beaudin
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Hanly
authors.forename: Marc J
authors.initials: MJ
authors.lastname: Poulin
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D018592:Cross-Over Studies; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000097:blood; D004311:Double-Blind Method; D006801:Humans; D000860:Hypoxia / Q000378:metabolism*; D019808:Losartan / Q000494:pharmacology*; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects*; D014443:Tyrosine / Q000031:analogs & derivatives / Q000097:blood; D014527:Uric Acid / Q000097:blood
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D014527:Uric Acid; D009569:Nitric Oxide; C002744:3-nitrotyrosine; D014443:Tyrosine; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine; D019808:Losartan