title: Early Postmenopausal Phase Is Associated With Reduced Prostacyclin-Induced Vasodilation That Is Reversed by Exercise Training: The Copenhagen Women Study.
abstract: The postmenopausal phase is associated with an accelerated rate of rise in the prevalence of vascular dysfunction and hypertension; however, the mechanisms underlying these adverse vascular changes and whether exercise training can reverse the decline in vascular function remains unclear. We examined the function of the vascular prostanoid system in matched pre- and postmenopausal women before and after 12 weeks of exercise training. Twenty premenopausal and 16 early postmenopausal (3.1±0.5 [mean±SE] years after final menstrual period) women only separated by 4 (50±0 versus 54±1) years of age were included. Before the training period, the vasodilator response to intra-arterial infusion of either the prostacyclin analog epoprostenol or acetylcholine was lower (≈13%-41%; P<0.05) in the postmenopausal compared with the premenopausal women. Acetylcholine infusion induced a similar release of prostacyclin (6-keto prostaglandin F1a). To elucidate the role of vasoconstrictor prostanoids, acetylcholine infusion was combined with the cyclooxygenase inhibitor ketorolac and here the vascular response to acetylcholine was reduced to a similar extent in pre- and postmenopausal women. Exercise training increased (P<0.05) the vasodilator response to epoprostenol (≈100%-150%) and acetylcholine (≈100%-120%) infusion in the postmenopausal group. These findings demonstrate that the early postmenopausal phase is associated with a marked reduction in vascular function. Despite of a reduced sensitivity to prostacyclin, the overall balance between vasodilator and vasoconstrictor prostanoids does not seem to be altered. Exercise training can reverse the decline in vascular sensitivity to epoprostenol and acetylcholine, suggesting that beneficial vascular adaptations with exercise training are preserved in recent postmenopausal women.
authors.affiliation: From the Department of Nutrition, Exercise and Sports (M.N., J.E., M.B.N., A.S.M., J.B., Y.H.) and Department of Biomedical Sciences (C.M.M., B.S.), University of Copenhagen, Denmark.
authors.forename: Michael
authors.initials: M
authors.lastname: Nyberg
authors.affiliation: From the Department of Nutrition, Exercise and Sports (M.N., J.E., M.B.N., A.S.M., J.B., Y.H.) and Department of Biomedical Sciences (C.M.M., B.S.), University of Copenhagen, Denmark.
authors.forename: Jon
authors.initials: J
authors.lastname: Egelund
authors.affiliation: From the Department of Nutrition, Exercise and Sports (M.N., J.E., M.B.N., A.S.M., J.B., Y.H.) and Department of Biomedical Sciences (C.M.M., B.S.), University of Copenhagen, Denmark.
authors.forename: Camilla M
authors.initials: CM
authors.lastname: Mandrup
authors.affiliation: From the Department of Nutrition, Exercise and Sports (M.N., J.E., M.B.N., A.S.M., J.B., Y.H.) and Department of Biomedical Sciences (C.M.M., B.S.), University of Copenhagen, Denmark.
authors.forename: Mads B
authors.initials: MB
authors.lastname: Nielsen
authors.affiliation: From the Department of Nutrition, Exercise and Sports (M.N., J.E., M.B.N., A.S.M., J.B., Y.H.) and Department of Biomedical Sciences (C.M.M., B.S.), University of Copenhagen, Denmark.
authors.forename: Alexander S
authors.initials: AS
authors.lastname: Mogensen
authors.affiliation: From the Department of Nutrition, Exercise and Sports (M.N., J.E., M.B.N., A.S.M., J.B., Y.H.) and Department of Biomedical Sciences (C.M.M., B.S.), University of Copenhagen, Denmark.
authors.forename: Bente
authors.initials: B
authors.lastname: Stallknecht
authors.affiliation: From the Department of Nutrition, Exercise and Sports (M.N., J.E., M.B.N., A.S.M., J.B., Y.H.) and Department of Biomedical Sciences (C.M.M., B.S.), University of Copenhagen, Denmark.
authors.forename: Jens
authors.initials: J
authors.lastname: Bangsbo
authors.affiliation: From the Department of Nutrition, Exercise and Sports (M.N., J.E., M.B.N., A.S.M., J.B., Y.H.) and Department of Biomedical Sciences (C.M.M., B.S.), University of Copenhagen, Denmark.
authors.forename: Ylva
authors.initials: Y
authors.lastname: Hellsten
mesh_terms: D000109:Acetylcholine / Q000008:administration & dosage*; D003430:Cross-Sectional Studies; D003718:Denmark; D004730:Endothelium, Vascular / Q000187:drug effects; D011464:Epoprostenol / Q000008:administration & dosage* / Q000378:metabolism; D015444:Exercise / Q000502:physiology*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007262:Infusions, Intravenous; D020910:Ketorolac / Q000008:administration & dosage*; D008875:Middle Aged; D017698:Postmenopause / Q000187:drug effects / Q000502:physiology*; D017697:Premenopause / Q000187:drug effects / Q000502:physiology; D018570:Risk Assessment; D016896:Treatment Outcome; D014664:Vasodilation / Q000187:drug effects*
chemical_list: D011464:Epoprostenol; D000109:Acetylcholine; D020910:Ketorolac
keywords: acetylcholine; epoprostenol; estrogens; hypertension; prostanoids