期刊
CARDIOVASCULAR RESEARCH
卷 77, 期 4, 页码 774-781出版社
OXFORD UNIV PRESS
DOI: 10.1093/cvr/cvm081
关键词
oestrogen receptor; myocardium; hypertrophy; hypertension
Aims The biological effects of oestrogens are mediated by two different oestrogen receptor (ER) subtypes, ER alpha and ER beta, which might play different, redundant, or opposing roles in cardiovascular disease. Previously, we have shown that the selective ER alpha agonist 16 alpha-LE2 improves vascular relaxation, attenuates cardiac hypertrophy, and increases cardiac output without lowering elevated blood pressure in spontaneously hypertensive rats (SHR). Because ER beta-deficient mice exhibit elevated blood pressure and since the ER beta agonist 8 beta-VE2 attenuated hypertension in aldosterone-salt-treated rats, we have now tested the hypothesis that the isotype-selective ER beta agonist 8 beta-VE2 might be capable of lowering elevated blood pressure in ovariectomized SHR. Methods and results Treatment of ovariectomized SHR with 8 beta-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 wet( as peripheral vascular resistance (-31.3 +/- 4.6%, P < 0.001 vs. placebo). 8 beta-VE2 enhanced aortic ER beta expression (+75.7 +/- 7.1%, P < 0.01 vs. placebo), improved NO-dependent vasorelaxation, augmented phosphorytation 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). 8 beta-VE2, in contrast to oestradiol, did not enhance cardiac a-myosin heavy chain expression. Conclusion Ligand-dependent activation of ER beta confers blood pressure lowering effects in SHR that are superior to those of 17 beta-estradiot or the ER alpha agonist 16 alpha-LE2 and attenuates cardiac hypertrophy primarily by a reduction of cardiac afterload without promoting uterine growth.
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