title: Aging enhances contraction to thromboxane A2 in aorta from female senescence-accelerated mice.
abstract: The time-course for aging-associated effects on vascular reactivity to U46619, a stable analogue of thromboxane A(2) (TXA(2)), was studied in aorta from female senescence-accelerated mice-prone (SAMP8), a murine model of accelerated senescence. SAMP8 and senescence-accelerated mice-resistant (SAMR1) were divided into three groups: 3-, 6- and 10-month-old. Contractile curves to U46619 (10(-9) to 10(-6) M) were performed in aortic rings in the absence or in the presence of nitric oxide synthase (NOS) inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME; 10(-4) M) and/or cyclooxygenase (COX) inhibitor indomethacin (10(-5) M). Protein and gene expression for COX-1 and COX-2 were determined by immunofluorescence and real-time PCR, respectively. Maximal contraction to U46619 was markedly higher in SAMP8 at all ages. In SAMR1, increases were seen at 10 months, while SAMP8 displays augmented contraction at 6 months, which was further increased at 10 months. L-NAME enhanced U46619 contractions in both 6-month-old groups, although the increase was higher on vessels from SAMR1 at this age. Indomethacin equally increased U46619 contractions in both 3-month-old groups, suggesting the production of vasodilator prostaglandin in young animals. In contrast, at 6 and 10 months indomethacin decreased U46619 contractions in both groups, indicating an aging-associated swap to a release of contractile prostanoids in aorta. In conclusion, aging enhances contractile responses to TXA(2) in aorta from female mice by a mechanism involving a decrease of NO production and increased action of contractile prostanoids. This process occurs earlier in SAMP8 mice, establishing these mice as good model to study cardiovascular aging in a convenient and standard time-course.
authors.affiliation: Departamento de Fisiología, Universitat de València, Valencia, Spain.
authors.forename: Susana
authors.initials: S
authors.lastname: Novella
authors.forename: Ana Paula
authors.initials: AP
authors.lastname: Dantas
authors.forename: Gloria
authors.initials: G
authors.lastname: Segarra
authors.forename: Laura
authors.initials: L
authors.lastname: Novensa
authors.forename: Magda
authors.initials: M
authors.lastname: Heras
authors.forename: Carlos
authors.initials: C
authors.lastname: Hermenegildo
authors.forename: Pascual
authors.initials: P
authors.lastname: Medina
mesh_terms: D000375:Aging / Q000235:genetics / Q000502:physiology*; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000502:physiology*; D051545:Cyclooxygenase 1 / Q000096:biosynthesis / Q000235:genetics; D051546:Cyclooxygenase 2 / Q000096:biosynthesis / Q000235:genetics; D005260:Female; D018507:Gene Expression Regulation, Developmental; D008565:Membrane Proteins / Q000096:biosynthesis / Q000235:genetics; D051379:Mice; D018384:Oxidative Stress / Q000502:physiology*; D012313:RNA / Q000096:biosynthesis / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D013928:Thromboxane A2 / Q000494:pharmacology*; D014661:Vasoconstriction / Q000187:drug effects*
chemical_list: D008565:Membrane Proteins; D013928:Thromboxane A2; D012313:RNA; C077623:Ptgs2 protein, mouse; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496512:Ptgs1 protein, mouse
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