Ovariectomy augments hypertension in aging female Dahl salt-sensitive rats

Ovariectomy augments hypertension in aging female Dahl salt-sensitive rats
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DOI:
10.1161/01.hyp.0000142893.08655.96
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发表时间:
2004-10-01
期刊:
影响因子:
8.3
通讯作者:
Sandberg, K
Sandberg, K
中科院分区:
医学1区
文献类型:
--
作者:
Hinojosa-Laborde, C;Craig, T;Sandberg, K

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卵巢切除(OVX)达尔盐敏感(DS)大鼠喂养低盐饮食是绝经后高血压的模型。除了雌激素的流失,衰老也会导致绝经后高血压。我们假设:(1)低盐饮食的雌性DS大鼠随着年龄的增长而变得高血压;(2)卵巢切除术加速了DS大鼠中由雌激素耗竭引起的年龄依赖性高血压;(3)这种高血压与1型血管紧张素受体(AT(1)R)数量(Bmax)增加相关。3 ~ 12个月时通过遥测监测血压,并通过Scatchard分析测定肾小球和肾上腺皮质中的AT 1 R Bmax。研究了三组DS大鼠:完整、OVX和17 β-雌二醇替代OVX(OVX + E)。在完整的大鼠中,老化至12个月导致高血压(159 +/- 6 mm Hg)和雌激素减少82%。12个月龄时,OVX组的血压显著高于OVX + E组(173 +/- 4 vs 150 +/- 8 mm Hg)。在4个月时,与完整和OVX + E相比,OVX增加了肾小球和肾上腺皮质的AT 1 R Bmax。老龄化也增加了AT 1 R Bmax在这些组织在完整的大鼠。总之,低盐饮食喂养的雌性DS大鼠随着年龄的增长而发生高血压,OVX加速了高血压的发生,而雌激素替代则减轻了高血压的发生。同时,AT(1)R受年龄和OVX的上调,这是由雌激素替代预防。这项研究表明,肾素血管紧张素系统的活性增加有助于高血压的发展,雌激素可以防止这一过程。
The ovariectomized (OVX) Dahl salt-sensitive (DS) rat fed a low-salt diet is a model of postmenopausal hypertension. In addition to estrogen loss, aging can also contribute to postmenopausal hypertension. We hypothesized that: (1) female DS rats on a low-salt diet become hypertensive with age; (2) ovariectomy accelerates age-dependent hypertension in the DS rat caused by estrogen depletion; and (3) this hypertension correlates with increased type 1 angiotensin receptor (AT(1)R) number (Bmax). Blood pressure was monitored by telemetry from 3 to 12 months and AT1R Bmax was determined by Scatchard analysis in glomeruli and adrenal cortex. Three groups of DS rats were studied: intact, OVX, and 17beta-estradiol-replaced OVX (OVX + E). In intact rats, aging to 12 months resulted in hypertension (159 +/- 6 mm Hg) and an 82% decrease in estrogen. Blood pressure in OVX was significantly higher than OVX + E through 12 months of age (173 +/- 4 versus 150 +/- 8 mm Hg). At 4 months, OVX increased AT1R Bmax compared with intact and OVX + E in both glomeruli and adrenal cortex. Aging also increased AT1R Bmax in these tissues in intact rats. In summary, female DS rats fed a low-salt diet have hypertension develop with age, that is accelerated by OVX and attenuated by estrogen replacement. Concurrently, AT(1)Rs are upregulated by age and OVX, which is prevented by estrogen replacement. This study suggests that an increased activity of the renin angiotensin system contributes to the development of hypertension, and estrogen protects against this process.