title: Atorvastatin protects against deleterious cardiovascular consequences induced by chronic intermittent hypoxia.
abstract: Chronic intermittent hypoxia (IH), a major component of obstructive sleep apnea (OSA), contributes to the high risk of cardiovascular morbidity. We have previously demonstrated that IH-induced oxidative stress is involved in the hypertension and in the hypersensitivity to myocardial infarction. However, the mechanisms underlying these cardiovascular alterations are still unclear, as well as the role of potential protective treatment. Atorvastatin has pleiotropic actions, including increasing nitric oxide (NO) bioavailability and reducing inflammation and oxidative damage. The aim of this study was to evaluate the beneficial effect of a two time course of this treatment against the deleterious cardiovascular consequences of IH. Rats were divided into two groups subjected to chronic IH or normoxic (N) exposure. IH consisted of repetitive one-minute cycles (with only 30 s of a 5% inspired O2 fraction) and was applied for eight hours during daytime, for 14 (simultaneous protocol) or 28 d (delayed protocol). Atorvastatin (10 mg/kg/ d) or its vehicle was administered during the 14 d simultaneous protocol or the last 14 d of the delayed protocol. For both protocols, systolic arterial pressure was significantly increased by 14 d IH exposure. Atorvastatin prevented this deleterious effect in the simultaneous protocol. Carotid artery compliance and endothelial function were significantly altered after 28 d but not after 14 d of IH exposure. Delayed atorvastatin administration preserved these vascular parameters. IH also increased hypersensitivity to myocardial infarction after 14 d exposure, and atorvastatin abolished this deleterious effect. IH also enhanced cardiac NADPH expression and decreased aortic superoxide dismutase activity after 14 d exposure. Atorvastatin significantly restored these activities. In conclusion, whereas IH rapidly increased blood pressure, myocardial infarction hypersensitivity and oxidative stress, compliance, endothelial function and the structural wall of the carotid artery were only altered after a longer IH exposure. Atorvastatin prevented all these deleterious cardiovascular effects, leading to a potentially novel pharmacological therapeutic strategy for OSA syndrome.
authors: UJF, Laboratoire HP2, Grenoble F-38000, France.
authors: Perle
authors: P
authors: Totoson
authors: Wassim
authors: W
authors: Fhayli
authors: Gilles
authors: G
authors: Faury
authors: Irina
authors: I
authors: Korichneva
authors: Sandrine
authors: S
authors: Cachot
authors: Marie
authors: M
authors: Baldazza
authors: Christophe
authors: C
authors: Ribuot
authors: Jean-Louis
authors: JL
authors: Pépin
authors: Patrick
authors: P
authors: Lévy
authors: Marie
authors: M
authors: Joyeux-Faure
mesh_terms: D000818:Animals; D000924:Anticholesteremic Agents / Q000008:administration & dosage*; D000069059:Atorvastatin; D001794:Blood Pressure; D002318:Cardiovascular Diseases / Q000209:etiology* / Q000503:physiopathology / Q000517:prevention & control*; D004195:Disease Models, Animal; D006538:Heptanoic Acids / Q000008:administration & dosage*; D000860:Hypoxia / Q000150:complications*; D018384:Oxidative Stress; D011758:Pyrroles / Q000008:administration & dosage*; D051381:Rats; D016896:Treatment Outcome
chemical_list: D000924:Anticholesteremic Agents; D006538:Heptanoic Acids; D011758:Pyrroles; D000069059:Atorvastatin