title: Endothelial relaxation mechanisms and oxidative stress are restored by atorvastatin therapy in ovariectomized rats.
abstract: The studies on hormone replacement therapy (HRT) in females with estrogen deficiency are not conclusive. Thus, non-estrogen therapies, such as atorvastatin (ATO), could be new strategies to substitute or complement HRT. This study evaluated the effects of ATO on mesenteric vascular bed (MVB) function from ovariectomized (OVX) female rats. Female rats were divided into control SHAM, OVX, and OVX treated with 17β-estradiol (EST) or ATO groups. The MVB reactivity was determined in organ chambers, vascular oxidative stress by dihydroethidine staining, and the expression of target proteins by western blot. The reduction in acetylcholine-induced relaxation in OVX rats was restored by ATO or EST treatment. The endothelium-dependent nitric oxide (NO) component was reduced in OVX rats, whereas the endothelium-derived hyperpolarizing factor (EDHF) component or prostanoids were not altered in the MVBs. Endothelial dysfunction in OVX rats was associated with oxidative stress, an up-regulation of iNOS and NADPH oxidase expression and a down-regulation of eNOS expression. Treatment with ATO or EST improved the NO component of the relaxation and normalized oxidative stress and the expression of those signaling pathways enzymes. Thus, the protective effect of ATO on endothelial dysfunction caused by estrogen deficiency highlights a significant therapeutic benefit for statins independent of its effects on cholesterol, thus providing evidence that non-estrogen therapy could be used for cardiovascular benefit in an estrogen-deficient state, such as menopause.
authors.affiliation: Department of Physiological Sciences, Federal University of Espirito Santo, Vitória, Espirito Santo, Brazil.
authors.forename: Izabela Facco
authors.initials: IF
authors.lastname: Caliman
authors.forename: Aline Zandonadi
authors.initials: AZ
authors.lastname: Lamas
authors.forename: Polyana Lima Meireles
authors.initials: PL
authors.lastname: Dalpiaz
authors.forename: Ana Raquel Santos
authors.initials: AR
authors.lastname: Medeiros
authors.forename: Glaucia Rodrigues
authors.initials: GR
authors.lastname: Abreu
authors.forename: Suely Gomes
authors.initials: SG
authors.lastname: Figueiredo
authors.forename: Lara Nascimento
authors.initials: LN
authors.lastname: Gusmão
authors.forename: Tadeu Uggere
authors.initials: TU
authors.lastname: Andrade
authors.forename: Nazaré Souza
authors.initials: NS
authors.lastname: Bissoli
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D000069059:Atorvastatin; D001685:Biological Factors / Q000494:pharmacology; D015153:Blotting, Western; D001835:Body Weight / Q000187:drug effects; D002784:Cholesterol / Q000097:blood; D051546:Cyclooxygenase 2 / Q000378:metabolism; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology*; D005260:Female; D006538:Heptanoic Acids / Q000494:pharmacology*; D008638:Mesenteric Arteries / Q000187:drug effects / Q000473:pathology; D019255:NADPH Oxidases / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D009929:Organ Size / Q000187:drug effects; D010052:Ovariectomy; D018384:Oxidative Stress / Q000187:drug effects*; D011453:Prostaglandins / Q000494:pharmacology; D011758:Pyrroles / Q000494:pharmacology*; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D014599:Uterus / Q000187:drug effects / Q000473:pathology; D014664:Vasodilation / Q000187:drug effects*
chemical_list: D001685:Biological Factors; D016861:Cyclooxygenase Inhibitors; D006538:Heptanoic Acids; D011453:Prostaglandins; D011758:Pyrroles; D017382:Reactive Oxygen Species; C067410:endothelium-dependent hyperpolarization factor; D002784:Cholesterol; D000069059:Atorvastatin; D019001:Nitric Oxide Synthase; D051546:Cyclooxygenase 2; D019255:NADPH Oxidases; D000109:Acetylcholine