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Treatment with Standard and Low Dose of Conjugated Equine Estrogen Differentially Modulates Estrogen Receptor Expression and Response to Angiotensin II in Mesenteric Venular Bed of Surgically Postmenopausal Hypertensive Rats.
Araujo, Priscila Xavier; Costa, Tiago Januário; Echem, Cinthya; Aparecida de Oliveira, Maria; Santos-Eichler, Rosangela Aparecida; Colli, Lucas Giglio; Jiménez-Altayó, Francesc; Vila, Elisabet; Akamine, Eliana Hiromi; Dantas, Ana Paula; Ceravolo, Graziela Scalianti; de Carvalho, Maria Helena Catelli.
Afiliação
  • Araujo PX; Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo, Brazil. (P.X.A., T.J.C., C.E., M.A.O., R.A.S.E., L.G.C., E.H.A., M.H.C.C.); Department of Physiological Sciences, State University of Londrina, Londrina, Brazil. (G.S.C.), Facultat de Medicina, Departament de Farm
  • Costa TJ; Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo, Brazil. (P.X.A., T.J.C., C.E., M.A.O., R.A.S.E., L.G.C., E.H.A., M.H.C.C.); Department of Physiological Sciences, State University of Londrina, Londrina, Brazil. (G.S.C.), Facultat de Medicina, Departament de Farm
  • Echem C; Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo, Brazil. (P.X.A., T.J.C., C.E., M.A.O., R.A.S.E., L.G.C., E.H.A., M.H.C.C.); Department of Physiological Sciences, State University of Londrina, Londrina, Brazil. (G.S.C.), Facultat de Medicina, Departament de Farm
  • Aparecida de Oliveira M; Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo, Brazil. (P.X.A., T.J.C., C.E., M.A.O., R.A.S.E., L.G.C., E.H.A., M.H.C.C.); Department of Physiological Sciences, State University of Londrina, Londrina, Brazil. (G.S.C.), Facultat de Medicina, Departament de Farm
  • Santos-Eichler RA; Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo, Brazil. (P.X.A., T.J.C., C.E., M.A.O., R.A.S.E., L.G.C., E.H.A., M.H.C.C.); Department of Physiological Sciences, State University of Londrina, Londrina, Brazil. (G.S.C.), Facultat de Medicina, Departament de Farm
  • Colli LG; Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo, Brazil. (P.X.A., T.J.C., C.E., M.A.O., R.A.S.E., L.G.C., E.H.A., M.H.C.C.); Department of Physiological Sciences, State University of Londrina, Londrina, Brazil. (G.S.C.), Facultat de Medicina, Departament de Farm
  • Jiménez-Altayó F; Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo, Brazil. (P.X.A., T.J.C., C.E., M.A.O., R.A.S.E., L.G.C., E.H.A., M.H.C.C.); Department of Physiological Sciences, State University of Londrina, Londrina, Brazil. (G.S.C.), Facultat de Medicina, Departament de Farm
  • Vila E; Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo, Brazil. (P.X.A., T.J.C., C.E., M.A.O., R.A.S.E., L.G.C., E.H.A., M.H.C.C.); Department of Physiological Sciences, State University of Londrina, Londrina, Brazil. (G.S.C.), Facultat de Medicina, Departament de Farm
  • Akamine EH; Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo, Brazil. (P.X.A., T.J.C., C.E., M.A.O., R.A.S.E., L.G.C., E.H.A., M.H.C.C.); Department of Physiological Sciences, State University of Londrina, Londrina, Brazil. (G.S.C.), Facultat de Medicina, Departament de Farm
  • Dantas AP; Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo, Brazil. (P.X.A., T.J.C., C.E., M.A.O., R.A.S.E., L.G.C., E.H.A., M.H.C.C.); Department of Physiological Sciences, State University of Londrina, Londrina, Brazil. (G.S.C.), Facultat de Medicina, Departament de Farm
  • Ceravolo GS; Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo, Brazil. (P.X.A., T.J.C., C.E., M.A.O., R.A.S.E., L.G.C., E.H.A., M.H.C.C.); Department of Physiological Sciences, State University of Londrina, Londrina, Brazil. (G.S.C.), Facultat de Medicina, Departament de Farm
  • de Carvalho MHC; Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo, Brazil. (P.X.A., T.J.C., C.E., M.A.O., R.A.S.E., L.G.C., E.H.A., M.H.C.C.); Department of Physiological Sciences, State University of Londrina, Londrina, Brazil. (G.S.C.), Facultat de Medicina, Departament de Farm
J Pharmacol Exp Ther ; 362(1): 98-107, 2017 07.
Article em En | MEDLINE | ID: mdl-28533289
ABSTRACT
Standard hormone therapy for menopausal women [conjugated equine estrogen (CEE) 0.625 mg] has been associated with increased risk of venous thrombosis. Regimens containing a lower CEE dose (0.30 mg) have been used clinically to decrease side effects of supraphysiologic doses of estrogen. In this study, we determined the effects of standard (SD) and low dose (LD) of CEE on venular function in ovariectomized (OVX) spontaneously hypertensive rats (SHR). Contractions by angiotensin-II (Ang-II 10 µM) in perfused mesenteric venular bed were markedly increased in OVX (21.5 ± 1.3 mmHg) compared with Sham (14.7 ± 1.1 mm Hg, P < 0.05). CEE-SD did not modify Ang-II responses in OVX, whereas CEE-LD restored Ang-II contraction to Sham levels. Endothelial nitric oxide synthase (eNOS) inhibition by L-NAME increased Ang-II contractions in Sham and CEE-LD and was without effect in venules of OVX SHR and CEE-SD. In OVX there was decreased NO generation in association with diminished eNOS phosphorylation and increased O2- generation in the venular wall. CEE-LD reverted the deleterious effects of ovariectomy. Although CEE-SD augmented eNOS phosphorylation in OVX, it was unable to increase NO levels, probably owing to its inability to reduce O2- Distinct effects by CEE-SD and CEE-LD parallel the differential modulation of Ang-II and estrogen receptors. Compared with Sham, CEE-LD increases Ang II receptor type 2, whereas CEE-SD modified ERß expression in the venous bed. Interestingly, both CEE doses increased G protein-coupled estrogen receptor in OVX. Our data suggest that estrogen dose is an important factor for venous function. Although CEE-LD reversed deleterious effects of OVX, CEE-SD showed null effects despite its ability to increase eNOS activity.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Circulação Esplâncnica / Angiotensina II / Receptores de Estrogênio / Pós-Menopausa / Estrogênios Conjugados (USP) Limite: Animals Idioma: En Ano de publicação: 2017 Tipo de documento: Article
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Circulação Esplâncnica / Angiotensina II / Receptores de Estrogênio / Pós-Menopausa / Estrogênios Conjugados (USP) Limite: Animals Idioma: En Ano de publicação: 2017 Tipo de documento: Article