Acute effects of 17β-estradiol on the rat heart

Eckstein, Nachman; Nadler, Etta; Barnea, Ofer; Shavit, Gabriel; Ayalon, Daniel

doi:10.1016/0002-9378(94)90109-0

Cited by 34 publications

(14 citation statements)

References 17 publications

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“…These results are in accordance with in vitro 28,29 and Figure 1. Effects of 17␤-E on cardiac output (A), ejection fraction (B), and calculated total peripheral resistance (C) in the intact circulation of female and male rats.…”

Section: Discussionsupporting

confidence: 92%

Acute Gender-Specific Hemodynamic and Inotropic Effects of 17β-Estradiol on Rats

Beyer

Yu²,

Hanke³

et al. 2001

Hypertension

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Abstract-Estrogen has cardioprotective effects. In addition to beneficial effects on lipid metabolism, estrogen affects the vascular tone and may reduce endothelial dysfunction. In the present study, we examined acute gender-specific hemodynamic and inotropic effects of 17␤-estradiol (17␤-E) versus the control situation in open-chest rats. In addition to measurements in the intact circulation, myocardial function was examined on the basis of isovolumic registration independent of peripheral vascular effects. Regarding the dose-dependent and gender-specific effects of 17␤-E, in female rats, 17␤-E (50, 100, or 200 ng/kg) increased cardiac output (CO) (26%, 43%, and 59% versus control animals) as a result of reduction in total peripheral resistance (TPR) (Ϫ13%, Ϫ18%, and Ϫ24%) without any effect on myocardial contractility (isovolumic left ventricular systolic pressure, Ϫ1%, 0%, and Ϫ6%). These vascular effects are less pronounced in male rats (for 200 ng/kg 17␤-E: CO, 34%; TPR, Ϫ14%). We investigated gender-specific effects of 200 ng/kg 17␤-E after pretreatment with the estrogen receptor (ER) antagonist ICI 182,780. ER blockade reduced the effects of estrogen in female rats (CO, 29%; TPR, Ϫ17%) and male rats (CO, 19%; TPR, Ϫ11%). Regarding the effects of 200 ng/kg 17␤-E after pretreatment with N G -nitro-L-arginine methyl ester, NO synthesis inhibition completely prevented the acute vascular effects of estrogen in female rats (CO, Ϫ4%; TPR, 1%). In addition, immunohistochemical staining revealed no gender-specific differences of the vascular ER distribution. 17␤-E caused an acute dose-dependent and gender-specific reduction in the afterload. ERs are involved in both genders in this vasodilative effect that is mediated by NO. This NO-mediated effect may explain in part the cardioprotective effect of estrogen. Key Words: estrogen Ⅲ receptors, estrogen Ⅲ nitric oxide Ⅲ hemodynamics Ⅲ contractility Ⅲ rats, Wistar T he incidence of coronary heart disease (CHD) is significantly lower in women than in men 1 and increases in women after surgically induced menopause 2 or after natural menopause. 3 Postmenopausal estrogen replacement therapy is a protective factor in the development of CHD. 4 Studies in primates have shown that estrogen therapy has a protective effect against atherosclerotic plaque development, 5,6 which cannot be fully explained by the beneficial effects of estrogen on lipid metabolism. 1 Estrogen also affects vascular tone. 7 Arterial tone is also of importance in the pathogenesis of atherosclerosis: in humans with CHD, there is an abnormal coronary vasoconstriction in response to acetylcholine (called endothelial dysfunction). 8 17␤-Estradiol (17␤-E) treatment 9 and endogenous estrogen 10 enhance endothelium-dependent relaxation in response to acetylcholine, and animal 6 and human 11,12 studies have demonstrated that estrogen can modulate or even abolish endothelial dysfunction in atherosclerotic vessels. This effect of 17␤-E was detectable only in atherosclerotic coronary arteries from women, not in tho...

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Section: Discussionsupporting

confidence: 92%

Acute Gender-Specific Hemodynamic and Inotropic Effects of 17β-Estradiol on Rats

Beyer

Yu²,

Hanke³

et al. 2001

Hypertension

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“…Thus, changes in heart rate can be due to ER-mediated changes, inasmuch as experiments on the isolated rat heart (44) show that 17-␤-estradiol decreased the heart rate, together with a dose-dependent negative chronotropic effect in the right atrium but not in the left atrium. Correspondingly, we have already demonstrated that the rat right atrium is the primary source of ANP release in response to volume expansion in association with heart rate reduction upon activation of oxytocin receptors (42,45).…”

Section: Discussionmentioning

confidence: 99%

Estrogen receptors activate atrial natriuretic peptide in the rat heart

Jankowski

Rachelska

Wang

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

118

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In this study, semiquantitative reverse transcription-PCR analysis showed that estrogen receptor ␣ (ER␣) and ␤ (ER␤) mRNAs are developmentally regulated in the rat heart. We found that ER␣ mRNA was low in all heart chambers of 4-day-old rats, but was elevated in the atria (6-to 18-fold) and ventricles (3-to 4-fold) of adult rats. Western blotting analysis confirmed that these differences were efficiently translated into 67-kDa ER␣ protein. ER␤ mRNA was expressed at its highest level in the left atrium and was 3-to 4-fold lower in other heart chambers of 4-day-old animals. In adult rats ER␤ was decreased dramatically in the left atrium (20-fold) and, to a lesser extent in the other heart chambers (2-to 4-fold). Significant ER changes occurred already in the first week after birth. Accordingly, estrogen regulation in cells from neonatal hearts, as reported in several studies, may not correspond to that occurring in fully differentiated adult hearts, because of an altered degree of ER expression. In adult rats, ovariectomy decreases atrial ER␣, the atria͞body weight ratio, and atrial natriuretic peptide (ANP) transcription. Treatment of ovariectomized rats with 17-␤-estradiol (25 g, 10 days, s.c.) reversed these changes. In addition, there was no effect of ovariectomy and 17-␤-estradiol supplementation on systolic blood pressure, but in ovariectomized rats a decreased heart rate followed 17-␤-estradiol administration. Similar to the effects on ER␣ in the atria, ovariectomy lowered plasma ANP levels, and 17-␤-estradiol administration restored ANP in the plasma of ovariectomized rats. Changes in plasma ANP correlated with changes in ANP content in the right atrium, as demonstrated by RIA. Increased ANP expression and secretion in response to ER␣ activation may be a protective mechanism in the heart. A trial natriuretic peptide (ANP) is a cardiac hormone produced predominantly in heart atria (1). It acts primarily on the ANP A receptor, that is, guanylyl cyclase, which converts GTP to cGMP. cGMP mediates the actions of ANP via protein kinase G. ANP plays an integral role in the regulation of hydromineral homeostasis under normal and pathological conditions, through potent biological effects, including vasorelaxation, diuresis, natriuresis, and reduction of venous return by a shift of plasma into the interstitium. The natriuretic and diuretic actions of ANP result from enhanced glomerular filtration and͞or decreased tubular reabsorption of sodium and water, suppression of renin, aldosterone, and vasopressin secretion, as well as antagonism of most of the peripheral and central effects of angiotensin II. The heart not only secretes ANP but also expresses ANP receptors, which control heart functions through cGMP production in cardiomyocytes and fibroblasts (2).The ANP gene is strongly activated in response to hypertrophic stimuli in the heart and prevents hypertrophy by inhibition of protein synthesis in cardiac myocytes via a cGMP-dependent process (3). Mice lacking ANP or its guanylyl cyclase A receptor exhibit marked ...

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“…Acute administration of estrogen in female or male patients improves vasodilator responses and ameliorates myocardial ischemia [4]. Also, acute administration of estrogen in dogs and isolated rat and rabbit hearts lowers coronary vascular resistance and enhances coronary blood flow [5]. Estrogen modulates vascular function by targeting estrogen receptor (ER) in endothelial cells (ECs) and vascular smooth muscle (VSM) [1, 2].…”

Section: Introductionmentioning

confidence: 99%

Estrogen, vascular estrogen receptor and hormone therapy in postmenopausal vascular disease

Khalil

2013

Biochemical Pharmacology

115

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Cardiovascular disease (CVD) is less common in premenopausal women than men of the same age or postmenopausal women, suggesting vascular benefits of estrogen. Estrogen activates estrogen receptors ERα, ERβ and GPR30 in endothelium and vascular smooth muscle (VSM), which trigger downstream signaling pathways and lead to genomic and non-genomic vascular effects such as vasodilation, decreased VSM contraction and growth and reduced vascular remodeling. However, randomized clinical trials (RCTs), such as the Women’s Health Initiative (WHI) and Heart and Estrogen/progestin Replacement Study (HERS), have shown little vascular benefits and even adverse events with menopausal hormone therapy (MHT), likely due to factors related to the MHT used, ER profile, and RCT design. Some MHT forms, dose, combinations or route of administration may have inadequate vascular effects. Age-related changes in ER amount, distribution, integrity and post-ER signaling could alter the vascular response to MHT. The subject’s age, preexisting CVD, and hormone environment could also reduce the effects of MHT. Further evaluation of natural and synthetic estrogens, phytoestrogens, and selective estrogen-receptor modulators (SERMs), and the design of appropriate MHT combinations, dose, route and 'timing' could improve the effectiveness of conventional MHT and provide alternative therapies in the peri-menopausal period. Targeting ER using specific ER agonists, localized MHT delivery, and activation of specific post-ER signaling pathways could counter age-related changes in ER. Examination of the hormone environment and conditions associated with hormone imbalance such as polycystic ovary syndrome may reveal the causes of abnormal hormone-receptor interactions. Consideration of these factors in new RCTs such as the Kronos Early Estrogen Prevention Study (KEEPS) could enhance the vascular benefits of estrogen in postmenopausal CVD.

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Acute effects of 17β-estradiol on the rat heart

Cited by 34 publications

References 17 publications

Acute Gender-Specific Hemodynamic and Inotropic Effects of 17β-Estradiol on Rats

Acute Gender-Specific Hemodynamic and Inotropic Effects of 17β-Estradiol on Rats

Estrogen receptors activate atrial natriuretic peptide in the rat heart

Estrogen, vascular estrogen receptor and hormone therapy in postmenopausal vascular disease

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