Effects of ovariectomy and 17β-estradiol treatment on the renin–angiotensin system, blood pressure, and endothelial ultrastructure

Xu, Xia; Xiao, Jiaying; Luo, Lixiang; Wang, Shan; Zhang, Jieping; Huang, Jianjun; Liu, Meilian; Liu, Chen-Geng; Xu, Ke; Li, Yuan‐Jian; Song, Huiping

doi:10.1016/j.ijcard.2007.08.041

Cited by 48 publications

(45 citation statements)

References 39 publications

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“…Ovariectomy does not change the adrenal aldosterone content, but estrogen treatment of OVX rats very significantly decreases aldosterone concentration, a finding consistent with the report of decreased Ang II-induced aldosterone release by estrogen replacement in OVX rats [21, 38]. That ovariectomy does not alter adrenal aldosterone levels in spite of enhanced AT 1 receptor expression may be explained by the concomitant decrease in circulating Ang II [62]. The estrogen-induced reduction in adrenal aldosterone is associated with a reversal of the ovariectomyinduced increase in AT 1 receptor expression.…”

Section: Discussionsupporting

confidence: 79%

Estrogen Reduces Aldosterone, Upregulates Adrenal Angiotensin II AT<sub>2</sub> Receptors and Normalizes Adrenomedullary Fra-2 in Ovariectomized Rats

Macova¹,

Armando²,

Zhou³

et al. 2008

Neuroendocrinology

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We studied the effect of ovariectomy and estrogen replacement on expression of adrenal angiotensin II AT₁ and AT₂ receptors, aldosterone content, catecholamine synthesis, and the transcription factor Fos-related antigen 2 (Fra-2). Ovariectomy increased AT₁ receptor expression in the adrenal zona glomerulosa and medulla, and decreased adrenomedullary catecholamine content and Fra-2 expression when compared to intact female rats. In the zona glomerulosa, estrogen replacement normalized AT₁ receptor expression, decreased AT_1B receptor mRNA, and increased AT₂ receptor expression and mRNA. Estrogen treatment decreased adrenal aldosterone content. In the adrenal medulla, the effects of estrogen replacement were: normalized AT₁ receptor expression, increased AT₂ receptor expression, AT₂ receptor mRNA, and tyrosine hydroxylase mRNA, and normalized Fra-2 expression and catecholamine content. We demonstrate that the constitutive adrenal expression of AT₁ receptors, catecholamine synthesis and Fra-2 expression are partially under the control of reproductive hormones. Our results suggest that estrogen treatment decreases aldosterone production through AT₁ receptor downregulation and AT₂ receptor upregulation. AT₂ receptor upregulation and modulation of Fra-2 expression may participate in the estrogen-dependent normalization of adrenomedullary catecholamine synthesis in ovariectomized rats. The AT₂ receptor upregulation and the decrease in AT₁ receptor function and in the production of the fluid-retentive, pro-inflammatory hormone aldosterone partially explain the protective effects of estrogen therapy.

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Section: Discussionsupporting

confidence: 79%

Estrogen Reduces Aldosterone, Upregulates Adrenal Angiotensin II AT<sub>2</sub> Receptors and Normalizes Adrenomedullary Fra-2 in Ovariectomized Rats

Macova¹,

Armando²,

Zhou³

et al. 2008

Neuroendocrinology

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“…In addition, there are studies showing the increased blood pressure due to estrogen deficiency in OVX rats. 34,35) Thus, the demonstration on whether renin inhibitor aliskiren could improve hypertension when benefits bone tissue of OVX animals has important clinical implications for postmenopausal women with bone loss, especially those with hypertension.…”

Section: Discussionmentioning

confidence: 99%

Renin Inhibition Improves Ovariectomy-Induced Osteoporosis of Lumbar Vertebra in Mice

Zhang

Yang

et al. 2014

Biological & Pharmaceutical Bulletin

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The skeletal renin-angiotensin system (RAS) is involved in the progression of osteoporosis and the active peptide within the RAS, angiotensin II (ANG II), has deleterious effects on bones. This study was performed to investigate whether suppression of the rate-limiting step of the RAS cascade by the renin inhibitor aliskiren has a benefit on trabecular bone in osteoporotic mice. A postmenopausal osteoporosis model was induced by bilateral ovariectomy. The ovariectomized (OVX) mice were treated with a low (5 mg/kg) or high (25 mg/kg) dose of aliskiren for 6 weeks. Micro-computed tomography was performed to detect trabecular bone parameters of lumbar vertebra and to obtain 3-dimensional (3D) images. Treatment with aliskiren markedly increased bone volume over total volume (p<0.05), trabecular bone number (p<0.05), connectivity density (p<0.05), and bone mineral density (p<0.05) and reduced trabecular bone separation (p<0.05) compared to vehicle-treated OVX mice. Similarly, the 3D images were consistent with the quantitative data that showed aliskiren could markedly reverse the ovariectomy-induced pathological changes of trabecular bone. Thus, this study indicated that the treatment of estrogen-deficient mice with aliskiren could markedly increase bone mass and improve trabecular bone structure, suggesting its potential application in treating postmenopausal osteoporosis.Key words renin-angiotensin system; aliskiren; bone; osteoporosis; ovariectomy The renin-angiotensin system (RAS) is a hormonal cascade that is thought to act as a master controller of blood pressure and fluid balance within the body.1) Within classical RAS, liver secreted angiotensinogen (AGT) is enzymatically cleaved to angiotensin (ANG) I by kidney-derived renin. ANG I is, hereafter, cleaved by angiotensin-converting enzyme (ACE) to the effector hormone ANG II. It is now evident that the components of RAS, in addition to the classical pathway, are expressed and act locally in multiple tissues, 2) such as insulin secretion, 3) glomerular sclerosis, 4) renal inflammation, 5) atherosclerosis, 6) cardiac hypertrophy 7) and brain disorders. 8)Recent studies showed that the components of RAS, such as renin, ACE, and ANG II receptors, are also expressed in the local milieu of bone. 9,10) Functional studies revealed that ANG II could stimulate the differentiation and activity of osteoclasts in vivo 11) and in vitro, 12) and aggravate the loss of bone minerals in rats with osteoporosis induced by estrogen deficiency, 11) furthermore, the ANG II type 1 receptor knockout mice showed high bone mass.13) In addition, we recently demonstrated that the local RAS in bone was involved in age-related osteoporosis of aging mice, 14) bone deteriorations of mice with either obstructive nephropathy 15) or type 1 diabetes, 16) and others elucidated the involvement of skeletal RAS in the process of fracture healing in a mouse femur fracture model. 17) Therefore, the local RAS displays important biological actions in bone tissue.Currently, besides the applications in the...

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“…The reduction in NPs after menopause could explain why hormone replacement therapy does not significantly reduce blood pressure in most postmenopausal women, which suggests that the loss of estrogens may not be the only component involved in the higher blood pressure in women after menopause. It has been suggested that estradiol protects rats from developing hypertension by increasing NO and NP levels while decreasing renin activity (15). …”

Section: Discussionmentioning

confidence: 99%

Effects of ovariectomy on the secretory apparatus in the right atrial cardiomyocytes of middle-aged mice

Souza

Oliveira

Curi

et al. 2014

Clinics

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OBJECTIVE: The aim of the present study was to evaluate the effects of ovariectomy on the secretory apparatus of natriuretic peptides in right atrial cardiomyocytes.METHODS:Nine-month-old mice underwent bilateral ovariectomy or sham surgery. The blood exam of the ovariectomized mice showed results consistent with castrated females. Systolic blood pressure was measured after ovariectomy (9 mo of age) and at the moment of sacrifice (12 mo of age). Fragments of the right atrium were collected and prepared for electron microscopy examination. The following variables were quantified: the quantitative density and area of the natriuretic peptide granules, the relative volume of euchromatin in the nucleus, the number of pores per 10 μm of the nuclear membrane and the relative volumes of the mitochondria and Golgi complex.RESULTS:The cardiomyocytes obtained from ovariectomized mice indicated that the quantitative density and the area of secretory granules of natriuretic peptides were significantly lower compared with the sham-operated mice. Furthermore, there was a decrease in the relative volume of euchromatin, a lower density of nuclear pores, and lower relative volumes of the mitochondria and Golgi complex in the ovariectomized mice compared with the sham-operated mice. These findings suggest a pool with a low turnover rate, i.e., low synthesis and elimination of natriuretic peptides.CONCLUSION:A lack of estrogen caused hypotrophy of the secretory apparatus in right atrial cardiomyocytes that could explain the weak synthesis of natriuretic peptides in mice. Furthermore, one of the mechanisms of blood pressure control was lost, which may explain, in part, the elevated blood pressure in ovariectomized mice.

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Effects of ovariectomy and 17β-estradiol treatment on the renin–angiotensin system, blood pressure, and endothelial ultrastructure

Cited by 48 publications

References 39 publications

Estrogen Reduces Aldosterone, Upregulates Adrenal Angiotensin II AT<sub>2</sub> Receptors and Normalizes Adrenomedullary Fra-2 in Ovariectomized Rats

Estrogen Reduces Aldosterone, Upregulates Adrenal Angiotensin II AT<sub>2</sub> Receptors and Normalizes Adrenomedullary Fra-2 in Ovariectomized Rats

Renin Inhibition Improves Ovariectomy-Induced Osteoporosis of Lumbar Vertebra in Mice

Effects of ovariectomy on the secretory apparatus in the right atrial cardiomyocytes of middle-aged mice

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