Article (Scientific journals)
Ligand-dependent activation of ER{beta} lowers blood pressure and attenuates cardiac hypertrophy in ovariectomized spontaneously hypertensive rats.
Jazbutyte, Virginija; Arias-Loza, Paula Anahi; Hu, Kai et al.
2008In Cardiovascular Research, 77 (4), p. 774-81
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Keywords :
Animals; Aorta/drug effects/metabolism; Blood Pressure/drug effects; Cardiomegaly/etiology/metabolism/physiopathology/prevention & control; Cell Adhesion Molecules/genetics/metabolism; Disease Models, Animal; Estradiol/analogs & derivatives/metabolism/pharmacology; Estrogen Receptor alpha/metabolism; Estrogen Receptor beta/agonists/metabolism; Female; Hemodynamics/drug effects; Hypertension/complications/drug therapy/metabolism/physiopathology; Ligands; Microfilament Proteins/genetics/metabolism; Myocardium/metabolism/pathology; Myosin Heavy Chains/genetics/metabolism; Ovariectomy; Phosphoproteins/genetics/metabolism; Rats; Rats, Inbred SHR; Uterus/drug effects/metabolism; Vasodilation/drug effects
Abstract :
[en] AIMS: The biological effects of oestrogens are mediated by two different oestrogen receptor (ER) subtypes, ERalpha and ERbeta, which might play different, redundant, or opposing roles in cardiovascular disease. Previously, we have shown that the selective ERalpha agonist 16alpha-LE2 improves vascular relaxation, attenuates cardiac hypertrophy, and increases cardiac output without lowering elevated blood pressure in spontaneously hypertensive rats (SHR). Because ERbeta-deficient mice exhibit elevated blood pressure and since the ERbeta agonist 8beta-VE2 attenuated hypertension in aldosterone-salt-treated rats, we have now tested the hypothesis that the isotype-selective ERbeta agonist 8beta-VE2 might be capable of lowering elevated blood pressure in ovariectomized SHR. METHODS AND RESULTS: Treatment of ovariectomized SHR with 8beta-VE2 for 12 weeks conferred no uterotrophic effects but lowered elevated systolic blood pressure (-38 +/- 5 mmHg, n = 31, P < 0.001 vs. placebo) as well as peripheral vascular resistance (-31.3 +/- 4.6%, P < 0.001 vs. placebo). 8beta-VE2 enhanced aortic ERbeta expression (+75.7 +/- 7.1%, P < 0.01 vs. placebo), improved NO-dependent vasorelaxation, augmented phosphorylation of the vasodilator-stimulated phosphoprotein in isolated aortic rings (P < 0.05 vs. placebo), increased cardiac output (+20.4 +/- 2.5%, P < 0.01 vs. placebo), and attenuated cardiac hypertrophy (-22.2 +/- 3.2%, p < 0.01 vs. placebo). 8beta-VE2, in contrast to oestradiol, did not enhance cardiac alpha-myosin heavy chain expression. CONCLUSION: Ligand-dependent activation of ERbeta confers blood pressure lowering effects in SHR that are superior to those of 17beta-estradiol or the ERalpha agonist 16alpha-LE2 and attenuates cardiac hypertrophy primarily by a reduction of cardiac afterload without promoting uterine growth.
Disciplines :
Cardiovascular & respiratory systems
Author, co-author :
Jazbutyte, Virginija
Arias-Loza, Paula Anahi
Hu, Kai
Widder, Julian
Govindaraj, Vijayakumar
von Poser-Klein, Christine
Bauersachs, Johann
Fritzemeier, Karl-Heinrich
Hegele-Hartung, Christa
Neyses, Ludwig ;  University of Luxembourg > Research Office
Ertl, Georg
Pelzer, Theo
Language :
English
Title :
Ligand-dependent activation of ER{beta} lowers blood pressure and attenuates cardiac hypertrophy in ovariectomized spontaneously hypertensive rats.
Publication date :
2008
Journal title :
Cardiovascular Research
ISSN :
0008-6363
Publisher :
Elsevier, Netherlands
Volume :
77
Issue :
4
Pages :
774-81
Peer reviewed :
Peer Reviewed verified by ORBi
Available on ORBilu :
since 16 October 2014

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