Sex Steroids, Cardiovascular Disease, and Hypertension

Reckelhoff, Jane F.

doi:10.1161/01.hyp.0000151825.36598.36

Cited by 148 publications

(121 citation statements)

References 83 publications

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“…On the other hand, the postmenopausal state with profound oestrogen deficiency results in a complex metabolic disorder. These alterations may be regarded as high-risk factors for ischaemic stroke, myocardial infarction (MI) and pulmonary emboli [10]. One study demonstrated that early menopause was significantly associated with increased CHD risk [11] and another study reported that women following bilateral oophorectomy had a higher possibility to have MI [12].…”

Section: Discussionmentioning

confidence: 99%

Detrimental effects of endogenous oestrogens on primary acute myocardial infarction among postmenopausal women

et al. 2013

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Objective Traditionally, oestrogens were considered to be protective for the cardiovascular system for premenopausal women. Therefore, we conducted a retrospective case-control study to examine the association between endogenous oestrogens and acute myocardial infarction (AMI) risk among postmenopausal women. Methods A case-control study was performed among 30 primary AMI patients and 60 control subjects. Baseline characteristics data was collected and endogenous sex hormones levels were determined using chemoluminescence and radioimmunoassay methods. Conditional logistic regression models were developed with adjustment for confounders. Results Compared with controls, the circulating oestrone, oestradiol, androstenedione and testosterone levels were significantly higher in AMI patients (P < 0.05) while the sex hormone binding globulin (SHBG) level was lower (P<0.05). Spearman correlation coefficients showed oestradiol was positively correlated with body mass index (BMI) and waist-to-hip ratio (WHR) in cases, but not in controls. In univariable conditional logistic regression models, oestrone, oestradiol, testosterone, WHR, BMI, diabetes and hypertension were all found to be positively associated with AMI (P<0.05). After adjusting for these factors, oestradiol (odds ratio (OR)04.75; 95 % confidence interval (CI)01.07-21.10; P00.04) and WHR (OR06.46; 95 % CI01.09-38.39; P00.04) continued to demonstrate strong positive associations with AMI. Conclusions A higher level of oestradiol was potentially associated with primary AMI risk among postmenopausal women.

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Section: Discussionmentioning

confidence: 99%

Detrimental effects of endogenous oestrogens on primary acute myocardial infarction among postmenopausal women

et al. 2013

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“…23 Limited NO release could also underlie the absence of a vasodilator response to 17␤-estradiol in HCAs. Despite the higher incidence of stroke, myocardial infarction, and dementia in postmenopausal women taking hormone replacement therapy, 24 virtually all in vitro studies published so far claim that estrogen induces vasodilation through endothelium-dependent or endothelium-independent mechanisms. 24 An alternative ex- planation for the absence of estrogen-induced vasodilation in HCAs, at least in women, is the change in estrogen receptor cellular localization during perimenopause.…”

Section: Discussionmentioning

confidence: 99%

“…Despite the higher incidence of stroke, myocardial infarction, and dementia in postmenopausal women taking hormone replacement therapy, 24 virtually all in vitro studies published so far claim that estrogen induces vasodilation through endothelium-dependent or endothelium-independent mechanisms. 24 An alternative ex- planation for the absence of estrogen-induced vasodilation in HCAs, at least in women, is the change in estrogen receptor cellular localization during perimenopause. 25 Furthermore, estrogen inactivates reactive oxygen species like the vasodilator H 2 O 2 26,27 and alters the AT 1 /AT 2 receptor ratio.…”

Section: Discussionmentioning

confidence: 99%

Nongenomic Effects of Aldosterone in the Human Heart

et al. 2005

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Abstract-Aldosterone exerts rapid "nongenomic" effects in various nonrenal tissues. Here, we investigated whether such effects occur in the human heart. Trabeculae and coronary arteries obtained from 57 heart valve donors (25 males; 32 females; 17 to 66 years of age) were mounted in organ baths. Aldosterone decreased contractility in atrial and ventricular trabeculae by maximally 34Ϯ3% and 15Ϯ4%, respectively, within 5 to 15 minutes after its application. The protein kinase C (PKC) inhibitor chelerythrine chloride, but not the mineralocorticoid receptor antagonists spironolactone and eplerenone, blocked this effect. Aldosterone also relaxed trabeculae that were prestimulated with angiotensin II (Ang II), and its negative inotropic effects were mimicked by hydrocortisone (at 10-fold lower potency) but not 17␤-estradiol. Aldosterone concentrations required to reduce inotropy were present in failing but not in normal human hearts. Previous exposure of coronary arteries to 1 mol/L aldosterone or 17␤-estradiol (but not hydrocortisone) doubled the maximum contractile response (E max ) to Ang II. ⌬E max correlated with extracellular signal-regulated kinase (ERK) 1/2 phosphorylation (PϽ0.01). Spironolactone and eplerenone did not block the potentiating effect of aldosterone. Studies in porcine renal arteries showed that potentiation also occurred at pmol/L aldosterone levels but not at 17␤-estradiol levels Ͻ1 mol/L. Aldosterone did not potentiate the ␣ 1 -adrenoceptor agonist phenylephrine. In conclusion, aldosterone induces a negative inotropic response in human trabeculae (thereby antagonizing the positive inotropic actions of Ang II) and potentiates the vasoconstrictor effect of Ang II in coronary arteries. These effects are specific and involve PKC and ERK 1/2, respectively. Furthermore, they occur in a nongenomic manner, and require pathological aldosterone concentrations.

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“…Investigations regarding the actions of testosterone have produced contradictory results (Kravariti et al 2005, Rosano et al 2005. For example, both vasodilatory (Webb et al 1999) and anti-vasodilatory effects have been observed (Hutchison et al 1997, Ceballos et al 1999 and testosterone may be involved in the development of some forms of experimental hypertension (Song et al 2004, Reckelhoff 2005. Endothelial cells have receptors for both oestradiol (Losordo et al 1994) and testosterone (Sierra-Ramirez et al 2004), by which these steroids can directly influence blood vessels and hence the development of vascular disease and hypertension.…”

Section: Introductionmentioning

confidence: 99%

Regulation of adrenomedullin release from human endothelial cells by sex steroids and angiotensin-II

Lj¹,

Rait²,

Nicholls³

et al. 2006

Journal of Endocrinology

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It is well documented that there are gender differences in the incidence and patterns of cardiovascular diseases but the reasons are unclear. Sex steroids may modulate the behaviour of vascular endothelial cells, which in turn act by paracrine processes to alter adjacent vascular smooth muscle activity. We hypothesised that the sex steroids alter the percentage of vascular endothelial cells that secrete the vasodilator peptide, adrenomedullin and modify the adrenomedullin-stimulating action of angiotensin-II. The percentage of adrenomedullinsecreting human aortic endothelial cells was determined using the cell immunoblot method. Cells were incubated with selected concentrations of angiotensin-II, oestradiol and testosterone alone and sex steroids in combination with angiotensin-II. Adrenomedullin mRNA expression in endothelial cells was quantified by real-time PCR. It was observed that at 4 h, angiotensin-II increased the percentage of adrenomedullin-secreting cells in a concentration-dependent manner. Testosterone at physiological concentrations was observed to increase the number of adrenomedullin-secreting cells whilst oestradiol had no effect. Addition of testosterone to angiotensin-II resulted in less than additive increases in the number of cells secreting adrenomedullin. Oestradiol reduced the angiotensin-II-induced increase in adrenomedullinsecreting cells. Adrenomedullin mRNA expression was significantly increased by testosterone and there was also a trend for an increase in adrenomedullin mRNA expression, which occurred when cells were incubated with angiotensin-II. Our results point to a complex interplay between the sex steroids and angiotensin-II in regulating adrenomedullin production by human endothelial cells, which may contribute to gender-related differences in vascular disease in humans.

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Sex Steroids, Cardiovascular Disease, and Hypertension

Cited by 148 publications

References 83 publications

Detrimental effects of endogenous oestrogens on primary acute myocardial infarction among postmenopausal women

Detrimental effects of endogenous oestrogens on primary acute myocardial infarction among postmenopausal women

Nongenomic Effects of Aldosterone in the Human Heart

Regulation of adrenomedullin release from human endothelial cells by sex steroids and angiotensin-II

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