17β-Estradiol downregulates tissue angiotensin-converting enzyme and ANG II type 1 receptor in female rats

Dean, Stephanie; Tan, Junhui; O'Brien, Edward R.; Leenen, Frans H. H.

doi:10.1152/ajpregu.00595.2004

Cited by 127 publications

(107 citation statements)

References 33 publications

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“…12,13,41 The cardiorenal protective effect of E2 seems to be complex and includes a wide range of regulatory system involvement with a role for the RAS strongly suggested in both human and animal studies. 30,[42][43][44][45][46] We reported previously that ACE inhibition abolishes hypertension in adult male IUGR offspring. 27 Furthermore, activation of the renal RAS but not peripheral RAS is associated with hypertension in adult male IUGR rats, 47 suggesting a role for the renal RAS in adult male IUGR hypertension.…”

Section: Discussionmentioning

confidence: 99%

Estrogen Protects Against Increased Blood Pressure in Postpubertal Female Growth Restricted Offspring

et al. 2007

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Abstract-Placental insufficiency in the rat results in intrauterine growth restriction and development of hypertension in prepubertal male and female growth-restricted offspring. However, after puberty, only male growth-restricted offspring remain hypertensive, whereas female growth-restricted offspring stabilize their blood pressure to levels comparable to adult female controls. Because female rats reach their maximum levels of estrogen at puberty, we hypothesize that estrogen may be a factor involved in the stabilization of blood pressure in adult female growth-restricted offspring. At 10 weeks of age, female control and growth-restricted offspring underwent ovariectomy or sham surgery and insertion of a telemetry probe. Mean arterial pressure was similar at 16 weeks of age between control (123Ϯ4 mm Hg) and growth-restricted offspring (122Ϯ2 mm Hg); however, ovariectomy led to a significant increase in blood pressure in growth-restricted offspring (140Ϯ2 mm Hg; PϽ0.05 versus intact counterpart) with no significant effect in controls (124Ϯ1 mm Hg). Estrogen replacement by subcutaneous minipellet initiated at 14 weeks of age in a subset of ovariectomized control and growth-restricted offspring reversed the effect of ovariectomy on blood pressure in growth-restricted offspring at 16 weeks of age (111Ϯ3 mm Hg; PϽ0.05 versus ovariectomized counterpart); renin angiotensin system blockade also abolished ovariectomy-induced hypertension in female growth-restricted offspring (106Ϯ2 mm Hg; PϽ0.05 versus ovariectomized counterpart). Therefore, sex differences are observed in this model of fetal programmed hypertension, and results from this study suggest that estrogen contributes to normalization of blood pressure in adult female growth-restricted offspring. Key Words: fetal programming Ⅲ intrauterine growth restriction Ⅲ ovariectomy Ⅲ estrogen Ⅲ renin angiotensin system H ypertension shows a clear age-related sex dimorphism. Nearly 1 in 3 adult Americans have hypertension. A higher percentage of men than women have hypertension until age 45 years, the percentage is similar from ages 45 to 54 years, and it becomes higher for women after that. 1 Thus, the risk of hypertension increases in women after the onset of menopause and continues to rise with age. 1-4 As a result, after menopause, a greater percentage of women have hypertension than age-matched men. 1,5,6 Epidemiological evidence suggests a regulatory role for estrogens in maintaining vascular function and structure. 7-9 Loss of ovarian function results in estrogen deficiency and increased risk for development of cardiovascular diseases, such as hypertension in postmenopausal women and women with ovarian surgical ablation. [7][8][9][10] In animal models of hypertension in which female rats are normotensive relative to their hypertensive male counterparts, ovariectomy induces hypertension. 11-14 Therefore, it seems that, while the ovaries are functional, women have a lower risk of cardiovascular disease than men, an observation supported by experimental studies.Alte...

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Section: Discussionmentioning

confidence: 99%

Estrogen Protects Against Increased Blood Pressure in Postpubertal Female Growth Restricted Offspring

et al. 2007

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“…Rings were stretched to 2 g of resting tension by means of 2 L-shaped stainless-steel wires inserted into the lumen and attached to the chamber and to an isometric force-displacement transducer (Letigraph 2000), respectively, as previously described. 32 The concentration-relaxation response curves to acetylcholine (ACh) (10 Ϫ9 mol/L to 10 Ϫ4 mol/L) were performed in rings pre-contracted by 10 Ϫ6 mol/L phenylephrine. The concentration-relaxation response curves to nitroprusside (10 Ϫ9 mol/L to 10 Ϫ5 mol/L) were performed in the dark in rings pre-contracted by 10 Ϫ6 mol/L phenylephrine.…”

Section: Vascular Reactivity Studiesmentioning

confidence: 99%

“…[2][3][4][5] Estrogens increase endothelial-derived NO, modulate the local tissue reninangiotensin system, and show antioxidant effects. [3][4][5][6][7][8][9][10] Long-term estrogen treatment improves endothelial dysfunction, through upregulation of endothelial nitric oxide synthase (eNOS), 11,12 posttranslational modulation of eNOS activity, 13 or nongenomic effects, including activation of NO synthesis. 14,15 However, despite the positive effects on vascular function found in cell culture, 12,14 ex vivo 15 and in vivo animal 16 -18 and short-term human 7,19 -21 studies, estrogen replacement therapy has failed to protect from cardiovascular diseases in large scale randomized controlled trials.…”

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confidence: 99%

Wine Polyphenols Improve Endothelial Function in Large Vessels of Female Spontaneously Hypertensive Rats

et al. 2008

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Abstract-Red wine polyphenols (RWPs) have been reported to prevent hypertension and endothelial dysfunction.Several individual RWPs exert estrogenic effects. We analyzed the possible in vivo protective effects on blood pressure and endothelial function of RWPs in female spontaneously hypertensive rats (SHR) and its relationship with ovarian function. RWPs (40 mg/kg by gavage) were orally administered for 5 weeks. Ovariectomized rats showed both increased isoprostaglandin F 2␣ excretion and aortic superoxide production and reduced relaxant response to acetylcholine and contraction to the endothelial nitric oxide synthase (eNOS) inhibitor L-NAME measured in the aorta but similar blood pressure, as compared with sham-operated rats. Moreover, in ovariectomized rats aortic eNOS expression was unchanged, whereas caveolin-1, angiotensin II receptor (AT)-1, and the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunits p22 phox and p47 phox expression was increased compared with sham-operated rats. In both ovariectomized and sham-operated SHR, RWPs reduced systolic blood pressure, urinary isoprostaglandin F 2␣ excretion, and aortic O 2 Ϫ production, improving the endothelium-dependent relaxant response to acetylcholine in SHR. These changes were associated with unchanged aortic eNOS expression, whereas caveolin-1 was increased and the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunits p22 phox and p47 phox expression was reduced. RWPs had no effect on the AT-1 overexpression found in ovariectomized animals. All these results suggest that a chronic treatment with RWPs reduces hypertension and vascular dysfunction through reduction in vascular oxidative stress in female SHR in a manner independent of the ovarian function. Key Words: red wine polyphenols Ⅲ spontaneously hypertensive rat Ⅲ endothelial dysfunction Ⅲ NADPH oxidase Ⅲ ovariectomy T he incidence of cardiovascular diseases among premenopausal women is lower than age-matched, men but it rises markedly after menopause. Blood pressure is also higher in men than in women at similar ages, 1 and this difference is also reduced or even inverted after menopause. The loss of estrogens has been suggested as a major risk factor for postmenopausal hypertension. Estrogen receptor (ER) subtypes ER␣ and ER␤ are expressed in endothelial and smooth muscle cells. [2][3][4][5] Estrogens increase endothelial-derived NO, modulate the local tissue reninangiotensin system, and show antioxidant effects. [3][4][5][6][7][8][9][10] Long-term estrogen treatment improves endothelial dysfunction, through upregulation of endothelial nitric oxide synthase (eNOS), 11,12 posttranslational modulation of eNOS activity, 13 or nongenomic effects, including activation of NO synthesis. 14,15 However, despite the positive effects on vascular function found in cell culture, 12,14 ex vivo 15 and in vivo animal 16 -18 and short-term human 7,19 -21 studies, estrogen replacement therapy has failed to protect from cardiovascular diseases in large scale randomized controlled ...

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“…9 -13 For example, estradiol inhibits renin release, whereas testosterone activates the renin-angiotensin system. 10,13,14 Also, previous reviews have provided detailed information on the effects of sex hormones on the vascular control mechanisms of blood pressure. 1,2,15 This brief report highlights the gender differences in vascular function and the genomic effects of sex hormones on endothelial cell and vascular smooth muscle (VSM) growth.…”

mentioning

confidence: 99%

Sex Hormones as Potential Modulators of Vascular Function in Hypertension

Khalil

2005

Hypertension

160

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Abstract-The greater incidence of hypertension in men and postmenopausal women compared with premenopausal women has suggested gender differences in vascular function. Vascular effects of the female sex hormones estrogen and progesterone and the male hormone testosterone have been described. Sex steroid receptors have been identified in vascular endothelium and smooth muscle. Interaction of sex hormones with cytosolic/nuclear receptors initiates long-term genomic effects that stimulate endothelial cell growth but inhibit smooth muscle proliferation. Activation of sex hormone receptors on the plasma membrane triggers nongenomic effects that stimulate endothelium-dependent vascular relaxation via NO-cGMP, prostacyclin-cAMP, and hyperpolarization pathways. Sex hormones also cause endothelium-independent inhibition of vascular smooth muscle contraction, [Ca 2ϩ ] i , and protein kinase C. These vasorelaxant/vasodilator effects suggested vascular benefits of hormone replacement therapy (HRT) during natural and surgically induced deficiencies of gonadal hormones. Although some clinical trials showed minimal benefits of HRT in postmenopausal hypertension, the lack of effect should not be generalized because it could be related to the type/dose of sex hormone, subjects' age, and other cardiovascular conditions. The prospect of HRT relies on continued investigation of the molecular mechanisms underlying the vascular effects of sex hormones and identification of compounds that specifically target the vascular sex hormone receptors. Naturally occurring hormones and phytoestrogens may be more beneficial HRT than synthesized compounds. Also, the type/dose, time of initiation, and duration of HRT should be customized depending on the subject's age and preexisting cardiovascular condition, and thereby enhance the outlook of sex hormones as potential modulators of vascular function in hypertension.

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17β-Estradiol downregulates tissue angiotensin-converting enzyme and ANG II type 1 receptor in female rats

Cited by 127 publications

References 33 publications

Estrogen Protects Against Increased Blood Pressure in Postpubertal Female Growth Restricted Offspring

Estrogen Protects Against Increased Blood Pressure in Postpubertal Female Growth Restricted Offspring

Wine Polyphenols Improve Endothelial Function in Large Vessels of Female Spontaneously Hypertensive Rats

Sex Hormones as Potential Modulators of Vascular Function in Hypertension

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