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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

Association of testosterone with estrogen abolishes the beneficial effects of estrogen treatment by increasing ROS generation in aorta endothelial cells

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Autor(es):
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Costa, Tiago J. [1] ; Ceravolo, Graziela S. [1, 2] ; dos Santos, Rosangela A. [1] ; de Oliveira, Maria Aparecida [1] ; Araujo, Priscila X. [1] ; Giaquinto, Luciana R. [1] ; Tostes, Rita C. [3] ; Akamine, Eliana H. [1] ; Fortes, Zuleica B. [1] ; Paula Dantas, Ana [4] ; Carvalho, Maria Helena C. [1]
Número total de Autores: 11
Afiliação do(s) autor(es):
[1] Univ Sao Paulo, Inst Biomed Sci, Dept Pharmacol, BR-05508900 Sao Paulo, SP - Brazil
[2] Univ Estadual Londrina, Dept Physiol Sci, Londrina - Brazil
[3] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Pharmacol, BR-05508900 Sao Paulo, SP - Brazil
[4] Inst Invest Biomed August Pi I Sunyer, Grp Atherosclerosis & Coronary Dis, Inst Clin Torax, Barcelona - Spain
Número total de Afiliações: 4
Tipo de documento: Artigo Científico
Fonte: AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY; v. 308, n. 7, p. H723-H732, APR 1 2015.
Citações Web of Science: 16
Resumo

Testosterone has been added to hormone replacement therapy to treat sexual dysfunction in postmenopausal women. Whereas estrogen has been associated with vascular protection, the vascular effects of testosterone are contradictory and the effects of its association with estrogen are largely unknown. In this study we determined the effects of testosterone associated with conjugated equine estrogen (CEE) on vascular function using a model of hypertensive postmenopausal female: ovariectomized spontaneously hypertensive rats. Female spontaneously hypertensive rats were divided into sham-operated, ovariectomized (OVX), and OVX treated for 15 days with either CEE alone (OVX + CEE) or associated with testosterone (OVX + CEE + T). Angiotensin II (ANG II)-induced contraction was markedly increased in aortic rings from OVX compared with sham-operated rats. CEE treatment restored ANG-II responses, a beneficial effect abrogated with CEE + T. CEE treatment also increased endothelium-dependent relaxation, which was impaired in OVX rats. This effect was lost by CEE + T. Treatment of aortas with losartan (ANG-II type-1 receptor antagonist) or apocynin (NADPH-oxidase inhibitor) restored the endothelium-dependent relaxation in OVX and CEE + T, establishing an interplay between ANG-II and endothelial dysfunction in OVX and CEE + T. The benefits by CEE were associated with downregulation of NADPH-oxidase subunits mRNA expression and decreased reactive oxygen species generation. The association of testosterone with CEE impairs the benefits of estrogen on OVX-associated endothelial dysfunction and reactive oxygen species generation in rat aorta by a mechanism that involves phosphorylation of the cytosolic NADPH-oxidase subunit p47(phox). (AU)

Processo FAPESP: 10/03608-1 - Tratamento de ratas espontaneamente hipertensas ovariectomizadas com conjugado estrogênio equino (Premarin)® associado à testosterona: caracterização dos efeitos vasculares
Beneficiário:Tiago Januário da Costa
Linha de fomento: Bolsas no Brasil - Mestrado