title: Gathering of aging and estrogen withdrawal in vascular dysfunction of senescent accelerated mice.
abstract: The aim of this work was to characterize a mouse model of experimental menopause and cardiovascular aging that closely reflects menopause in women. Senescence accelerated mouse (SAM)-Resistant type 1 (SAMR1, n=30) and SAM-Prone type 8 (SAMP8, n=30) were separated at 5months of age into three groups: 1) sham-operated (Sham); 2) ovariectomized (Ovx); and 3) ovariectomized chronically-treated with estrogen (Ovx+E2). Contractile responses to KCl (60mM) and thromboxane A(2) were greater in aorta from SAMP8 mice compared with SAMR1 in all groups. Neither ovariectomy nor estrogen replacement modified the contractile responses from SAMR1 mice. Conversely, in Ovx SAMP8 the increased maximal contractions were reversed by estrogen treatment. Rings with endothelium from all SAMR1 groups showed a greater relaxation to acetylcholine than SAMP8 groups. In SAMR1, endothelium-dependent relaxation was not altered in Ovx or Ovx+E2 groups. Rings from Ovx SAMP8 showed a decreased maximal response to acetylcholine compared to Sham SAMP8. Estrogen replacement restored the response to acetylcholine altered by ovariectomy. Nitric oxide inhibition by L-NAME markedly reduced acetylcholine responses in all groups, but this effect was less pronounced in SAMP8 and Ovx groups (determined by area under the curve reduction). These results indicate that SAMP8 exhibit a significant decreased endothelium-dependent and NO-mediated relaxation and increased vasoconstrictor responses that are potentiated by the lack of estrogen. Because these responses are closely in agreement with vascular dysfunction observed in menopausal women, we propose SAMP8 Ovx as a new model to concomitantly study the effects of aging and menopause in female mice.
authors: Department of Physiology, University of Valencia, Valencia, Spain.
authors: Susana
authors: S
authors: Novella
authors: Ana Paula
authors: AP
authors: Dantas
authors: Gloria
authors: G
authors: Segarra
authors: Laura
authors: L
authors: Novensà
authors: Carlos
authors: C
authors: Bueno
authors: Magda
authors: M
authors: Heras
authors: Carlos
authors: C
authors: Hermenegildo
authors: Pascual
authors: P
authors: Medina
mesh_terms: D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D000109:Acetylcholine / Q000494:pharmacology; D019588:Aging, Premature / Q000503:physiopathology*; D000818:Animals; D001011:Aorta / Q000378:metabolism; D001808:Blood Vessels / Q000503:physiopathology*; D015536:Down-Regulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004958:Estradiol / Q000494:pharmacology; D015914:Estrogen Replacement Therapy; D004967:Estrogens / Q000378:metabolism* / Q000494:pharmacology; D005260:Female; D066298:In Vitro Techniques; D051379:Mice; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000037:antagonists & inhibitors; D010052:Ovariectomy; D044244:Receptors, Thromboxane A2, Prostaglandin H2 / Q000378:metabolism; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D004791:Enzyme Inhibitors; D004967:Estrogens; D044244:Receptors, Thromboxane A2, Prostaglandin H2; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D009569:Nitric Oxide; D004958:Estradiol; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000109:Acetylcholine; D019331:NG-Nitroarginine Methyl Ester