RESUMEN
We summarize convincing evidence that future cardiovascular disease (CVD) risk increases one-fold to four-fold for women with a history of pregnancy complicated by hypertensive disorders, gestational diabetes, fetal growth restriction, placental abruption and preterm birth. A concomitant occurrence of two or more complications in the same pregnancy further potentiates the risk. These women should be informed of their future CVD risks during the postpartum check-up taking place after delivery, and also, if needed, treated, for example, for persisting high blood pressure. In these women with high blood pressure, check-up should take place within 7-10 days, and if severe hypertension, within 72 h. Women without diagnostic signs and symptoms should be examined for the first time 1-2 years postpartum and then at intervals of 2-3 years for a complete CVD risk profile including clinical and laboratory assessments. Women should be informed for future CVD risks and their effective prevention with healthy lifestyle factors. Combined oral contraceptives should be avoided or used with caution. If laboratory or other clinical findings indicate, then vigorous treatments consisting of non-medical and medical (antihypertensives, statins, antidiabetic and anti-obesity therapies) interventions should be initiated early with liberal indications and with ambitious therapeutic goals. Low-dose aspirin and menopausal hormone therapy should be used in selected cases. Active control and treatment policies of these women with pregnancy-related risks will likely result in decreases of CVD occurrence in later life.
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Enfermedades Cardiovasculares , Hipertensión , Nacimiento Prematuro , Embarazo , Femenino , Recién Nacido , Humanos , Enfermedades Cardiovasculares/etiología , Enfermedades Cardiovasculares/prevención & control , Enfermedades Cardiovasculares/epidemiología , Nacimiento Prematuro/prevención & control , Placenta , Factores de RiesgoRESUMEN
OBJECTIVE: We compared the trends of hormone therapy (HT) use among women with and without a history of pre-eclampsia. METHODS: This national cohort study consisted of women with a pre-eclamptic pregnancy (n = 31,688) or a normotensive pregnancy (n = 91,726) (controls) during 1969-1993. The data on their use of HT during 1994-2019 were traced from the National Medicine Reimbursement Register. RESULTS: Both women with a history of pre-eclampsia and controls initiated HT at a mean age of 49.9 years. Cumulative HT™ use during the total follow-up did not differ between the groups (31.1% vs. 30.6%, p = 0.066). However, HT use in previously pre-eclamptic women was less common in 1994-2006 (20.2% vs. 22.4%, p < 0.001) and more common in 2007-2019 (22.1% vs. 21.1%, p < 0.001) than in controls. This trend was also seen in the annual changes of HT starters. Women with a history of pre-eclampsia used HT for a shorter time (6.3 vs. 7.1 years, p < 0.001). CONCLUSIONS: In contrast to controls, HT use in previously pre-eclamptic women increased during the last half of the follow-up. This may reflect the changes in the international recommendations, the increased awareness of pre-eclampsia-related cardiovascular risk later in life and the aim to diminish this risk with HT.
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Preeclampsia , Embarazo , Femenino , Humanos , Persona de Mediana Edad , Preeclampsia/epidemiología , Estudios de Cohortes , Terapia de Reemplazo de Estrógeno/efectos adversos , Finlandia/epidemiología , Presión SanguíneaRESUMEN
Stress urinary incontinence (SUI) affects millions of women worldwide. Pelvic floor muscle training is the first-line treatment for SUI, and if this fails, midurethral sling surgery has become the gold-standard treatment. More recently, complications from midurethral mesh slings, particularly chronic pain and dyspareunia, have become a major concern. Although traditional SUI treatments, such as colposuspension and fascia slings, are used, the future of SUI treatment likely will rely on less invasive alternatives. Modern bulking agents could have the potential to become a first-line treatment for SUI, but further long-term studies are needed. Patients should be involved in decision-making prior to any surgery to ensure that they are aware of the risks and also any reasonable treatment alternatives. Furthermore, the effectiveness of a procedure should be balanced with its invasiveness and possible risks to provide women individually with the best possible treatment option.
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Cabestrillo Suburetral , Incontinencia Urinaria de Esfuerzo/cirugía , Femenino , Humanos , Procedimientos Quirúrgicos UrológicosRESUMEN
We examined the associations between childhood growth and bone properties among women at early old age. Early growth in height predicted greater bone area and higher bone mineral mass. However, information on growth did not improve prediction of bone properties beyond that predicted by body size at early old age. INTRODUCTION: We examined the associations between body size at birth and childhood growth with bone area, bone mineral content (BMC), and areal bone mineral density (aBMD) in early old age. METHODS: A subgroup of women (n = 178, mean 60.4 years) from the Helsinki Birth Cohort Study, born 1934-1944, participated in dual-energy X-ray absorptiometry (DXA) measurements of the lumbar spine and hip. Height and weight at 0, 2, 7, and 11 years, obtained from health care records, were reconstructed into conditional variables representing growth velocity independent of earlier growth. Weight was adjusted for corresponding height. Linear regression models were adjusted for multiple confounders. RESULTS: Birth length and growth in height before 7 years of age were positively associated with femoral neck area (p < 0.05) and growth in height at all age periods studied with spine bone area (p < 0.01). Growth in height before the age of 7 years was associated with BMC in the femoral neck (p < 0.01) and birth length and growth in height before the age of 7 years were associated with BMC in the spine (p < 0.05). After entering adult height into the models, nearly all associations disappeared. Weight gain during childhood was not associated with bone area or BMC, and aBMD was not associated with early growth. CONCLUSIONS: Optimal growth in height in girls is important for obtaining larger skeleton and consequently higher bone mass. However, when predicting bone mineral mass among elderly women, information on early growth does not improve prediction beyond that predicted by current height and weight.
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Envejecimiento/fisiología , Densidad Ósea/fisiología , Desarrollo Óseo/fisiología , Desarrollo Infantil/fisiología , Absorciometría de Fotón/métodos , Anciano , Antropometría/métodos , Estatura/fisiología , Tamaño Corporal/fisiología , Estudios de Cohortes , Femenino , Cuello Femoral/fisiología , Estudios de Seguimiento , Humanos , Recién Nacido , Vértebras Lumbares/fisiología , Persona de Mediana EdadRESUMEN
Coronary artery disease (CAD) is still the most common killer of western women. Coronary arteries, expressing estrogen receptors, are a target for estrogen action. Prior to the Women's Health Initiative (WHI) study, postmenopausal hormone therapy (HT) was widely advocated for primary prevention of CAD, but such use was criticized after the WHI publication. However, new data accumulated in the USA and in Europe indicate that the use of estradiol-based HT regimens does not endanger the heart, but rather, it significantly reduces the incidence of CAD events and mortality. This effect may be related to the presence of hot flushes before HT initiation, because they may indicate a greater responsiveness of the cardiovascular system to HT. To get maximal cardioprotective efficacy of HT, a woman should initiate HT as soon as symptoms occur, and preferably within the first 10 postmenopausal years. Recent guidelines for optimal use of HT recommend pauses of HT at 1-2-year intervals to see whether hot flushes and other symptoms still persist. However, new data question the safety of this policy, because acute withdrawals of estradiol from the circulation may predispose to potentially fatal CAD events. All these data support modernized guidelines for optimal HT use.
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Cardiotónicos/administración & dosificación , Enfermedad de la Arteria Coronaria/prevención & control , Terapia de Reemplazo de Estrógeno/métodos , Estrógenos/administración & dosificación , Posmenopausia/efectos de los fármacos , Esquema de Medicación , Estradiol/administración & dosificación , Femenino , Sofocos/tratamiento farmacológico , Humanos , Persona de Mediana EdadRESUMEN
SUMMARY: The association between lactation and bone size and strength was studied in 145 women 16 to 20 years after their last parturition. Longer cumulative duration of lactation was associated with larger bone size and strength later in life. INTRODUCTION: Pregnancy and lactation have no permanent negative effect on maternal bone mineral density but may positively affect bone structure in the long term. We hypothesized that long lactation promotes periosteal bone apposition and hence increasing maternal bone strength. METHODS: Body composition, bone area, bone mineral content, and areal bone mineral density of whole body and left proximal femur were assessed using DXA, and cross-sectional area and volumetric bone mineral density of the left tibia shaft were measured by pQCT in 145 women (mean age 48 years, range 36-60 years) 16 to 20 years after their last parturition. Hip (HSI) and tibia strength indexes (TBSI) were calculated. Medical history and lifestyle factors including breastfeeding patterns and durations were collected via a self-administered questionnaire. Weight change during each pregnancy was collected from personal maternity tracking records. RESULTS: Sixteen to 20 years after the last parturition, women who had breastfed in total more than 33 months in their life, regardless of the number of children, had greater bone strength estimates of the hip (HSI = 1.92 vs. 1.61) and the tibia (TBSI = 5,507 vs. 4,705) owing to their greater bone size than mothers who had breastfed less than 12 months (p < 0.05 for all). The differences in bone strength estimates were independent of body height and weight, menopause status, use of hormone replacement therapy, and present leisure time physical activity level. CONCLUSION: Breastfeeding is beneficial to maternal bone strength in the long run.
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Densidad Ósea/fisiología , Huesos/anatomía & histología , Lactancia/fisiología , Absorciometría de Fotón/métodos , Adulto , Antropometría/métodos , Composición Corporal , Huesos/fisiología , Lactancia Materna , Femenino , Fémur/anatomía & histología , Fémur/fisiología , Humanos , Persona de Mediana Edad , Estudios Retrospectivos , Tibia/anatomía & histología , Tibia/fisiología , Factores de TiempoRESUMEN
AIM: To study a possible association between the potent vasodilatory nitric oxide and postmenopausal hot flushes. METHODS: We compared the release of nitric oxide in 150 recently menopausal women reporting no (n = 23), mild (n = 34), moderate (n = 30), or severe (n = 63) hot flushes. Plasma samples, collected after a 48-h arginine-poor diet, were assessed for the metabolites of nitric oxide (NOx), using the Griess reaction. RESULTS: Levels of NOx showed no association with the severity of hot flushes. Furthermore, no relationships with individual hot flushes and serum levels of estradiol or high-sensitivity C-reactive protein were detected. CONCLUSIONS: These preliminary data indicate that nitric oxide appears not to be a factor in hot flushes and might not be related to their etiology. Since a fasting plasma NOx measurement may not reflect what happens at the time of the hot flush episode, in future studies there should be an attempt to assess nitric oxide release during a concomitant hot flush.
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Sofocos/sangre , Nitratos/sangre , Nitritos/sangre , Posmenopausia/sangre , Proteína C-Reactiva/metabolismo , Estradiol/sangre , Femenino , Humanos , Persona de Mediana Edad , Óxido Nítrico/sangre , Índice de Severidad de la Enfermedad , Estadísticas no ParamétricasRESUMEN
INTRODUCTION: Menopausal hot flushes may affect the responses of various vascular risk factors to hormone therapy (HT). We compared the responses of biochemical markers for cardiovascular diseases to HT in recently postmenopausal women with tolerable or intolerable hot flushes. METHODS: Healthy, non-smoking freshly postmenopausal women (n = 150) with no previous HT use were studied. Seventy-two women reported intolerable hot flushes (> or =7 moderate/severe episodes/day) and 78 women tolerable hot flushes (< or =3 mild episodes/day). The participants were treated in randomized order with either transdermal estradiol gel (1 mg), oral estradiol valerate (2 mg) with or without medroxyprogesterone acetate (5 mg), or placebo for 6 months. Treatment-induced changes in lipids, lipoproteins, apolipoproteins, sex hormone binding globulin (SHBG) and high-sensitivity C-reactive protein were compared. The trial is registered in the US National Institutes of Health Clinical Research Registry (no. NCT00668603). RESULTS: Pretreatment hot flush status was not related to the responses of these markers to different forms of HT. However, when all active regimens were evaluated together as a post-hoc analysis, 7/10 markers showed a tendency toward greater beneficial changes in women with intolerable hot flushes. Furthermore, in women with intolerable hot flushes and with HT use, the increases in SHBG (Spearman's rho = - 0.570, p < 0.001) were related to the reductions in hot flushes during the use of HT. CONCLUSIONS: Hot flushes appear to be no significant determinant for the responses of vascular markers to HT use.
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Enfermedades Cardiovasculares/sangre , Terapia de Reemplazo de Estrógeno/métodos , Sofocos/tratamiento farmacológico , Posmenopausia/sangre , Administración Cutánea , Administración Oral , Apolipoproteína A-I/sangre , Apolipoproteínas B/sangre , Biomarcadores/sangre , Proteína C-Reactiva/análisis , Enfermedades Cardiovasculares/diagnóstico , Estradiol/administración & dosificación , Estrógenos/administración & dosificación , Femenino , Sofocos/sangre , Humanos , Acetato de Medroxiprogesterona/administración & dosificación , Persona de Mediana Edad , Posmenopausia/efectos de los fármacos , Globulina de Unión a Hormona Sexual/análisisRESUMEN
The gynecologist is often the only physician a woman consults on a regular basis and therefore gynecologists play a crucial role in the primary prevention of cardiovascular disease. Cardiovascular risk factors in women entering the menopausal transition are poorly managed, partly due to the fact that primary-care physicians, gynecologists and cardiovascular physicians often fail to identify cardiovascular risk factors and also undertreat women at increased cardiovascular risk. Furthermore, most women are not well informed about their cardiovascular risk profile. Gynecologists and cardiologists should work together as a team in identifying and managing cardiovascular risk factors. European cardiologists and gynecologists have written a Consensus statement and a short guide to help menopause physicians to assess and manage the cardiovascular risk in women.
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Enfermedades Cardiovasculares/diagnóstico , Enfermedades Cardiovasculares/prevención & control , Ginecología , Rol del Médico , Posmenopausia , Enfermedades Cardiovasculares/epidemiología , Terapia de Reemplazo de Estrógeno , Femenino , Humanos , Posmenopausia/fisiología , Prevención Primaria , Medición de RiesgoAsunto(s)
Densidad Ósea/fisiología , Huesos/anatomía & histología , Lactancia/fisiología , Femenino , HumanosRESUMEN
OBJECTIVES: Tibolone is often taken concurrently with soy. Tibolone, soy and equol-producing capacity each affect vascular health, whereas their concomitant effects are unknown. We studied the effects of soy on sex steroids and vascular inflammation markers in long-term tibolone users. METHODS: Postmenopausal women (n = 110) on tibolone were screened with a soy challenge to find 20 equol producers and 20 non-producers. All women were treated for 8 weeks in a cross-over trial with soy (52 g of soy protein containing 112 mg of isoflavones) or placebo. Serum estrone, 17beta-estradiol, testosterone, androstenedione, dehydroepiandrosterone sulfate (DHEAS), sex hormone binding globulin (SHBG), C-reactive protein (CRP), vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), and platelet-selectin (P-selectin) were assessed. RESULTS: Soy decreased (7.1%) the estrone level, significantly (12.5%) only in equol producers (from 80.2 +/- 10.8 to 70.3 +/- 7.0 pmol/l; p = 0.04). Testosterone was reduced (15.5%; from 586 +/- 62.6 to 495 +/- 50.1 pmol/l, p = 0.02) during soy treatment, and more markedly in equol producers than non-producers (22.1% vs. 10.0%). No changes appeared in SHBG, CRP or ICAM-1, but VCAM-1 increased (9.2%) and P-selectin decreased (10.3%) during soy treatment. CONCLUSIONS: Soy modified the concentrations of estrone, testosterone and some endothelial markers. Equol production enforced these effects. Soy supplementation may be clinically significant in tibolone users.
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Moduladores de los Receptores de Estrógeno/uso terapéutico , Isoflavonas/metabolismo , Norpregnenos/uso terapéutico , Posmenopausia , Proteínas de Soja/administración & dosificación , Proteína C-Reactiva/análisis , Estudios Cruzados , Equol , Estrona/sangre , Femenino , Humanos , Molécula 1 de Adhesión Intercelular/sangre , Persona de Mediana Edad , Selectina-P/sangre , Globulina de Unión a Hormona Sexual/análisis , Testosterona/sangre , Molécula 1 de Adhesión Celular Vascular/sangreRESUMEN
Results from the recent randomized clinical trials indicating that hormone therapy (HT) does not provide cardiovascular protection, but potentially harm are in profound disagreement with the sound evidence from numerous observational and experimental studies. While the observational studies have mainly assessed symptomatic recently menopausal women, the randomized trials have studied symptomless elderly postmenopausal women with established coronary heart disease or various risk factors for cardiovascular disease. Therefore, the recent trials have only revealed that HT does not provide secondary cardiovascular benefits. Since primary cardiovascular benefits of HT are rational but not yet proven in clinical trials, new studies are in demand. Until more data from recently menopausal symptomatic women are available, we need to base our decisions on existing evidence and good clinical practice. Although the potential of HT to provide cardiovascular benefits is decreased by advancing age and time since menopause, this should not preclude the use of individualized HT in younger postmenopausal women. (Reprod Med Biol 2005; 4: 1- 6).
RESUMEN
The exact mechanisms by which estrogens protect against occlusive vascular disorders are not known. One possibility could be an effect on vascular endothelial vasoactive compounds, such as vasodilatory prostacyclin (PGI2) and vasoconstrictory endothelin (ET-1). Here we report on the effect of 17 beta-estradiol on the synthesis of PGI2 and ET-1 in cultured human umbilical vein endothelial cells. These cells were incubated in the absence (control) and presence of 17 beta-estradiol (0.001-1 mumol/L) for 3-24 h with serum (10%) or without serum. The release of PGI2, as assessed by its metabolite 6-keto-prostaglandin F1 alpha, and that of ET-1, were assessed by RIA. 17 beta-Estradiol (0.01-0.1 mumol/L) predissolved in ethanol (final concentration, 0.01%) increased PGI2 production by 26-30% in endothelial cells incubated without serum. This increase in PGI2 production was enhanced up to 66% when 17 beta-estradiol (1 mumol/L) was encapsulated within beta-cyclodextrin. The stimulation of PGI2 production was detectable after 12 h of incubation. The 17 beta-estradiol-induced stimulation of PGI2 production was blocked in dose-dependent manner by antiestrogenic tamoxifen. 17 beta-Estradiol failed to affect the production of PGI2 if the endothelial cells were incubated with serum and had no effect on ET-1 production under any conditions. 17 beta-Estradiol-induced stimulation of vasodilatory and antiaggregatory PGI2 production without a concomitant change in vasoconstrictory ET-1 production may provide one explanation for the ability of estradiol to maintain vascular health and protect against vascular disorders.
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Endotelinas/biosíntesis , Endotelio Vascular/metabolismo , Epoprostenol/biosíntesis , Estradiol/farmacología , beta-Ciclodextrinas , 6-Cetoprostaglandina F1 alfa/biosíntesis , Células Cultivadas , Ciclodextrinas , Portadores de Fármacos , Endotelio Vascular/efectos de los fármacos , Estradiol/administración & dosificación , Humanos , Tamoxifeno/farmacología , Venas UmbilicalesRESUMEN
OBJECTIVE: To determine whether transdermal hormone replacement therapy modifies the ability of plasma or serum to regulate the synthesis of prostacyclin and that of endothelin-1 by cultured human umbilical vein endothelial cells. DESIGN: Prospective, randomized study. SETTING: Department of Obstetrics and Gynecology, Helsinki University Central Hospital. PATIENT(S): Thirteen postmenopausal women with climacteric symptoms. INTERVENTIONS: Transdermal 17beta-E2 (50 microg/d) continuously combined with norethisterone acetate, (250 microg/d) on days 15-28 of the treatment cycles for 6 months. MAIN OUTCOME MEASURE(S): Levels of prostacyclin's metabolite 6-keto-prostaglandin F1alpha and of endothelin-1 released by cultured human umbilical vein endothelial cells. RESULT(S): Plasma and serum during the E2-only phase of hormone replacement therapy enhanced prostacyclin production by 20% +/- 8% (mean +/- SEM) and 23% +/- 11%, respectively. Plasma or serum taken during the E2 + norethisterone acetate phase failed to affect prostacyclin production. Hormone replacement therapy induced no change in the capacity of plasma or serum to release endothelin-1. CONCLUSION(S): Transdermal hormone replacement therapy during the E2-only phase increased the capacity of plasma and serum to enhance production of vasoprotective prostacyclin in human vascular endothelial cells, without affecting production of endothelin-1. Addition of norethisterone acetate prevented this stimulation.
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Sangre , Endotelio Vascular/metabolismo , Epoprostenol/biosíntesis , Estradiol/administración & dosificación , Terapia de Reemplazo de Estrógeno , Progestinas/administración & dosificación , 6-Cetoprostaglandina F1 alfa/metabolismo , Administración Cutánea , Células Cultivadas , Endotelina-1/metabolismo , Estradiol/sangre , Femenino , Hormona Folículo Estimulante/sangre , Humanos , Noretindrona/administración & dosificación , Noretindrona/análogos & derivados , Acetato de Noretindrona , Posmenopausia , Estudios Prospectivos , Venas UmbilicalesRESUMEN
OBJECTIVE: To determine if hormone replacement therapy (HRT) modifies the ability of plasma or serum to regulate the synthesis of vasodilatory prostacyclin and that of vasoconstrictive endothelin-1 by cultured human umbilical vein endothelial cells. DESIGN: Plasma and serum collected before and during the sixth treatment cycle of HRT from 13 healthy postmenopausal women were added to cultured endothelial cells. SETTING: Helsinki University Central Hospital, Department of Obstetrics and Gynecology, Helsinki, Finland. PATIENTS: Thirteen postmenopausal women (> or = 1 year since their last menstruation, FSH level > 40 mIU/mL [conversion factor to SI unit, 1.00], clear vasomotor symptoms) that suffered from incapacitating menopausal symptoms necessitating the initiation of HRT were studied. INTERVENTIONS: A combined regimen consisting of 2 mg oral E2 for 12 days followed by 2.0 mg oral E2 + 1.0 mg norethisterone acetate for 10 days and 1.0 mg E2 for 6 days. MAIN OUTCOME MEASURES: The releases of prostacyclin, as assessed by its metabolite 6-keto-prostaglandin F1 alpha, and that of endothelin-1 by cultured human umbilical vein endothelial cells in the presence of 10% plasma or 10% serum collected from the study subjects. RESULTS: Hormone replacement therapy enhanced the ability of plasma to stimulate prostacyclin production by 21% +/- 6% (mean +/- SEM) during the E2 + norethisterone acetate phase and tended to do so also during the E2-only phase (11% +/- 10%) but caused no change in endothelin-1 release. In contrast, HRT decreased the ability of serum to stimulate prostacyclin production by 12% +/- 5% during the E2-only phase and increased that of endothelin-1 by 8% +/- 4% during the E2 + norethisterone acetate phase. CONCLUSION: Because plasma flushes endothelial cells in vivo, our data on the HRT-induced stimulation of the capacity of plasma to enhance the production of vasoprotective prostacyclin without a concomitant change in endothelin-1 release in cultured human umbilical vein endothelial cells may provide one new explanation for the cardiovascular protection of HRT.
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Fenómenos Fisiológicos Sanguíneos , Endotelinas/metabolismo , Endotelio Vascular/metabolismo , Epoprostenol/metabolismo , Terapia de Reemplazo de Estrógeno , Estrógenos/farmacología , Células Cultivadas , Endotelio Vascular/citología , Femenino , Humanos , Persona de Mediana Edad , Plasma/fisiología , Venas UmbilicalesRESUMEN
To study the effect of hirudin on endothelial cell prostacyclin (PGI2) and endothelin-1 (ET-1) production, we cultured human umbilical vein endothelial cells (HUVECs), stimulated them with 0.00001-10 kU/l of hirudin for 12-24 hours, and measured by radioimmunoassays the concentrations of 6-ketoprostaglandinF1 alfa (6-keto, a metabolite of PGI2) and ET-1 in the incubation medium. In incubation medium containing 10% serum hirudin stimulated PGI2-production dose-dependently. The lowest stimulatory hirudin concentration was 0.001 kU/l, which increased the concentration of 6-keto by 10.8 +/- 4.4% (mean +/- S.E) (p < 0.01). The greatest stimulation rate (28.6 +/- 6.2%, p < 0.001) was obtained with the highest hirudin concentration (10 kU/l), when the culture medium contained 10% human serum. The PGI2-stimulating activity was exaggerated in the absence of serum, when 1 kU/l of hirudin increased PGI2-production by 59.7 +/- 6.2% (p < 0.001, n = 14). Stimulation of PGI2 appeared after 12 hour incubation. Hirudin had no effect on the conversion of exogenous arachidonic acid to 6-keto or on the production of ET-1. We thus conclude that hirudin stimulates PGI2-production through de novo protein synthesis. Stimulation of PGI2-production by hirudin may contribute to its antithrombotic activity, since PGI2 favours vasodilatation and attenuates platelet aggregation.
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Anticoagulantes/farmacología , Endotelina-1/biosíntesis , Endotelio Vascular/efectos de los fármacos , Epoprostenol/biosíntesis , Hirudinas/farmacología , Células Cultivadas , Endotelio Vascular/citología , Humanos , Estimulación QuímicaRESUMEN
Prostacyclin (PGI2), a powerful vasodilatory prostanoid, and endothelin-1 (ET-1), a potent vasoconstrictive peptide, are produced by vascular endothelial cells. We show that human serum (10%) caused a 3.2-fold stimulation both in PGI2 and ET-1 synthesis in human endothelial cells cultured from umbilical veins, and human plasma (10%) stimulated productions of both 1.6- and 1.7-fold, respectively. In addition, releasates from thrombin-activated platelets (20 x 10(9) platelets/l) caused a 1.9-fold increase in PGI2 and a 1.4-fold increase in the ET-1 synthesis. Releasates from frozen-thawed and sonicated platelets (20 x 10(9) platelets/l) caused a 3.6-fold increase in PGI2 release but did not affect ET-1 production. We thus conclude that, in normal situation, endothelial stimulating activity present in plasma perhaps plays a role in the regulation of endothelial function, whereas platelet-derived activity in serum may be important at site of thrombosis.
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Fenómenos Fisiológicos Sanguíneos , Plaquetas/fisiología , Endotelinas/biosíntesis , Endotelio Vascular/metabolismo , Epoprostenol/biosíntesis , Plaquetas/efectos de los fármacos , Células Cultivadas , Femenino , Humanos , Masculino , Trombina/farmacologíaRESUMEN
OBJECTIVES: To elucidate the mechanisms by which estrogens protect against occlusive vascular disorders, we studied the effect of 17 beta-estradiol on the production of prostacyclin (PGI2) and nitric oxide (NO) in primary cultures of human umbilical vein endothelial cells (HUVECs). METHODS: To study the effect of 17 beta-estradiol on PGI2 production, HUVECs were incubated in the absence and presence of 17 beta-estradiol (0.01-10 nmol/l) encapsulated within beta-cyclodextrin for 12 h in serum-free medium. To study the effect of 17 beta-estradiol (100 nmol/l) on maximal calcium-dependent NO production, we used different approaches. First, HUVECs were incubated with 2 mumol/l calcium ionophore A23187 with or without 17 beta-estradiol (100 nmol/l) for 24 h in serum-free medium. Second, HUVECs were preincubated with or without 17 beta-estradiol (100 nmol/l) for 12 h in medium supplemented with 2% fetal calf serum, and thereafter incubated in serum-free medium with 2 mumol/l of A23187 and with 100 nmol/l of 17 beta-estradiol (cells which contained 17 beta-estradiol during the preincubation period as well as cells which did not) or without it (only cells which did not contain 17 beta-estradiol during the preincubation period) for 6 h or 24 h. RESULTS: 17 beta-Estradiol (0.1 nmol/l) increased the concentration of 6-keto-prostaglandin F1 alpha, a stable metabolite of PGI2 in the incubation medium, by 16%, and no further increase occurred with higher 17 beta-estradiol concentrations. The stimulation was prevented by tamoxifen. 17 beta-Estradiol did not affect NO production in any of our experiments measured as accumulation of nitrate and nitrite in the experimental medium. CONCLUSIONS: The stimulatory effect on PGI2 production of physiological concentrations of 17 beta-estradiol, shown now for the first time, may provide one explanation for the ability of 17 beta-estradiol to protect against occlusive vascular disorders.
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Endotelio Vascular/efectos de los fármacos , Epoprostenol/sangre , Estradiol/farmacología , Óxido Nítrico/sangre , Técnicas de Cultivo , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Resistencia Vascular/efectos de los fármacosRESUMEN
It is well documented that postmenopausal estrogen/progestin therapy (HRT) protects women against cardiovascular disorders. However, the mechanism(s) by which this protection is mediated remains largely unresolved, because beneficial effects of estrogen on the blood lipid profile account for only 20-30% of the overall protection. Growing evidence suggests that estrogen has direct effects on the blood vessel wall indicating that vascular endothelium may play a key role in mediating these effects by producing vasoactive factors, such as prostacyclin (PGI2), nitric oxide (NO) and endothelin-1 (ET-1). In vitro estrogen stimulates endothelial PGI2 and NO production, whereas ET-1 production is not affected. Moreover, in vivo studies indicate that estrogen and HRT increase PGI2 and NO production, whereas ET-1 production decreases. These effects are evidently mediated through estrogen receptors in endothelial cells. Thus, estrogen and HRT lead to the dominance of vasodilatory and antiaggregatory agents released by the endothelial cells. This may be an important new mechanism in the cardiovascular protection mediated by estrogen and HRT.
Asunto(s)
Endotelina-1/biosíntesis , Endotelio Vascular/efectos de los fármacos , Epoprostenol/biosíntesis , Terapia de Reemplazo de Estrógeno , Óxido Nítrico/biosíntesis , Progestinas/uso terapéutico , Secuencia de Aminoácidos , Animales , Quimioterapia Combinada , Endotelio Vascular/metabolismo , Femenino , Humanos , Datos de Secuencia MolecularRESUMEN
OBJECTIVES: Equol, a gut bacterial metabolite of the isoflavone daidzein, has been associated with beneficial health effects. Recent studies indicate that women with intestinal capacity to convert daidzein to equol also have the capacity to alter steroid metabolism and bioavailability of estrogens. METHODS: We evaluated whether individual equol production capability, while not consuming soy supplement, was associated with lower blood pressure in postmenopausal women using tibolone. In addition, in a randomized, placebo-controlled, cross-over trial we assessed the effect of soy supplementation on blood pressure in both equol-producing (n = 20) and non-equol-producing (n = 20) women using tibolone. Blood pressure was recorded with a validated oscillometric technique. RESULTS: The circulating equol levels rose 20-fold in the equol producers and 1.9-fold in the non-equol producers. At baseline, systolic blood pressure (129.9 +/- 2.6 vs. 138.5 +/- 3.1 mmHg, p = 0.02), diastolic blood pressure (72.2 +/- 1.5 vs. 76.6 +/- 1.3 mmHg, p = 0.01) and mean arterial blood pressure (93.5 +/- 1.7 vs. 99.9 +/- 1.8 mmHg, p = 0.007) were lower in equol producers compared to non-equol producers. Soy supplementation had no effect on blood pressure in either group, whereas the baseline differences persisted. CONCLUSIONS: Postmenopausal women using tibolone characterized as equol producers had lower blood pressure compared to non-equol producers. Soy supplementation for 2 months had no blood pressure-lowering effect.