Associations of salivary aldosterone levels during pregnancy with maternal blood pressure and birth weight-for-gestational age in a Mexico City birth cohort.

OBJECTIVE: To determine associations of maternal salivary aldosterone with blood pressure (BP) in pregnancy and infant birth weight-for-gestational age (BWGA). METHODS: We measured maternal salivary aldosterone, BP and BWGA z-scores in 471 Mexico City pregnancy cohort participants and performed multivariable linear regression of BP and BWGA on log-aldosterone levels. RESULTS: Log-aldosterone was positively associated with diastolic BP (ß = 0.12 95% CI: 0.04, 0.21). There were no main effects of log-aldosterone on BWGA. However, we detected an interaction between log-aldosterone and BP in association with BWGA; higher log-aldosterone was associated with lower BWGA in the lowest (ß = -0.12, 95% CI: -0.26, 0.02) and highest (ß = -0.12, 95% CI: -0.29, 0.06) BP tertiles. In contrast, in the middle BP tertile the association was positive (ß = 0.09, 95% CI: -0.02, 0.20), p for interaction = 0.03. CONCLUSION: Higher maternal salivary aldosterone is positively associated with diastolic BP and may affect fetal growth differently depending on concurrent maternal blood pressure.

Longitudinal patterns of breastfeeding and its association with adiposity and subjective indicators of satiety/appetite in the first 2 years of life.

Evidence about the association between breastfeeding and its duration with growth, appetite and satiety indicators, and adiposity in low and middle-income countries facing nutritional transition is scarce. The aim of this study was to evaluate the association between longitudinal patterns of breastfeeding (exclusive [EBF] and continued [CBF]) with adiposity and growth, and the mediating role of appetite and satiety indicators in these associations in Mexican children during the first 2 years of life. Information from 378 mother-child pairs from the MAS-Lactancia birth cohort was analysed. Information was collected at birth and at months 1, 3, 6, 9, 12, 18 and 24 of life. Duration of EBF and CBF was computed. Linear mixed models were used to assess the association of EBF and CBF with growth and adiposity. Path analysis was used for mediation analysis. Compared with the reference group (EBF duration <1 month), males with >3 to ≤6 months of EBF had less abdominal circumference (ß = -0.66, p = 0.05), Z-score weight-for-length (ß = -0.17, p = 0.19) and length-for-age (ß = -0.49, p < 0.01). Participants without CBF beyond 6 months had higher BMI Z-score (ß = 0.19, p < 0.01), abdominal circumference (ß = 0.62, p < 0.01) and skinfold sum (ß = 0.80, p = 0.09), and o difference in length-for-age. For EBF, mediation was confirmed for satiety responsiveness on the association with BMI Z-Score, for food fussiness for the association with abdominal circumference and length-for-age Z-score, and enjoyment of food on the association with length-for-age Z-score. For CBF, mediation was confirmed for food fussiness in the association with length-for-age. This study suggests that a longer exposure to EBF and CBF is associated with lower adiposity in children under 2 years of age, and that this association could be partially mediated by appetite and satiety indicators.

Reducing Sodium Consumption in Mexico: A Strategy to Decrease the Morbidity and Mortality of Cardiovascular Diseases.

Hypertension (HTN) and cardiovascular diseases (CVD) are important public health problems in Mexico. High sodium intake is linked to high blood pressure and increased risk of developing CVD. International organizations suggest consuming <2 g of sodium/day; however, the Mexican population consumes amounts above what is recommended: 3.1 g/day. Although efforts have been made to mitigate this problem, interventions are needed to improve cardiovascular health. This policy brief offers a short review of the current sodium consumption situation in Mexico and the importance of why decision makers should consider actions to reduce consumption. Recommendations to reduce sodium/salt intake include: Reformulation of ultra-processed-foods, promote the use warning labels, communication campaign, reduce the use of table salt, and monitor sodium intake.

Prenatal and Early Childhood Exposure to Lead and Repeated Measures of Metabolic Syndrome Risk Indicators From Childhood to Preadolescence.

Background: Exposure to lead (Pb) during the early life stages has been associated with the development of metabolic syndrome (MetS). Longitudinal studies of Pb exposure in critical developmental windows in children are limited. Methods: Our study included 601 mother-child dyads from the PROGRESS (Programming Research in Obesity, Growth, Environment and Social Stressors) birth cohort. Blood lead levels (BLLs) were assessed during the second and third gestational trimesters, in cord blood at delivery, and at ages 1, 2, and 4 years. Bone lead levels in the patella and tibia were assessed at 1 month postpartum and evaluated in separate models. To account for cumulative exposure (prenatal, postnatal, and cumulative), we dichotomized the BLLs at each stage visit and determined the following: "higher" if a BLL was at least once above the median (HPb) and "lower" if all BLLs were below the median (LPb). We analyzed fasting glucose, HbA1c, triglycerides (TGs), total cholesterol (TC), high-density lipoprotein cholesterol (cHDL), low-density lipoprotein cholesterol (cLDL), body mass index, waist circumference (WC), body fat percentage, and systolic (SBP) and diastolic blood pressure (DBP) at two study visits between 6 and 12 years of age and created cutoff points based on the clinical guidelines for each indicator. Mixed effects models were used to analyze each outcome longitudinally for each BLL score, adjusting for child's sex, size for gestational age, child's age, maternal parity, mother's age, and socioeconomic status. Results: We observed associations for HPb exposure and TC in all stages (OR = 0.53, 95%CI = 0.32-0.86) and postnatally (OR = 0.59, 95%CI = 0.36-0.94) and for prenatal HPb and TGs (OR = 0.65, 95%CI = 0.44-0.95). HPb at all stages was associated with WC (OR = 0.27, 95%CI = 0.08-0.86), BMI (OR = 0.33, 95%CI = 0.11-0.99), SBP (OR = 0.53, 95%CI = 0.32-0.85), and DBP (OR = 0.57, 95%CI = 0.34-0.95). Pb levels in the patella were associated with cHDL (OR = 1.03, 95%CI = 1.00-1.07) and those in the tibia with TGs (OR = 0.95, 95%CI = 0.91-0.99). Conclusion: Early life exposure to Pb may alter early indicators of MetS. A follow-up of these children will allow for more definition on the impact of longer-term exposures.

Infant feeding, appetite and satiety regulation, and adiposity during infancy: a study design and protocol of the 'MAS-Lactancia' birth cohort.

INTRODUCTION: The prevalence of childhood obesity has risen dramatically in recent years. A proportion of this burden has been attributed to factors that occur during the first 1000 days of life such as genetic predisposition, breast feeding and complementary feeding. Although the mechanisms by which these factors affect weight and adiposity are less well understood, appetite and satiety regulation may be a key to understanding them. This cohort study aims to investigate the role of appetite and satiety regulation as a mediator in the association between infant feeding practices and genetic polymorphisms with children's growth, adiposity and metabolic risk factors. METHODS AND ANALYSIS: 'MAS-Lactancia' (the first word means 'more' and is also an acronym in Spanish for 'Appetite and Satiety Mechanisms', the second word is 'breastfeeding') is an open, ongoing, prospective birth cohort that began the enrolment in 2016 of mother-child pairs affiliated to the Mexican Social Security Institute and that live in the city of Cuernavaca, Mexico. Pregnant women between 16-week and 22-week gestation are followed during the second half of their pregnancies, at birth and throughout their infant's first 48 months of life (at 1 month, 3 months, 6 months, 9 months, 12 months, 18 months, 24 months, 36 months and 48 months) at the clinic and at-home visits that include questionnaires, anthropometric measurements and biospecimen collection. The main exposure variables are infant feeding (breast feeding and complementary feeding) and genetic polymorphisms (fat mass and obesity-associated, leptin and adiponectin genes). Outcome variables include infant's growth, adiposity and metabolic risk factors. We will conduct longitudinal models and path analyses to identify the potential mediating role of satiety and appetite indicators (leptin, adiponectin, insulin concentrations, appetite and satiety perception). ETHICS AND DISSEMINATION: The study protocol, data collection instruments, consent forms and procedures were approved by the institutional review boards of the National Institute of Public Health and the Mexican Social Security Institute in Mexico. Findings will be disseminated through conferences, peer-reviewed publications and meetings with stakeholders.

Pro-Inflammatory Diet Is Associated with Adiposity during Childhood and with Adipokines and Inflammatory Markers at 11 Years in Mexican Children.

There is limited evidence about the inflammatory potential of diet in children. The aim of this study was to evaluate the association between the Children's Dietary Inflammatory Index (C-DII) from 5 to 11 years with adiposity and inflammatory biomarkers in Mexican children. We analyzed 726 children from a birth cohort study with complete dietary information and measurements to evaluate adiposity at 5, 7 and 11 y and 286 children with IL-6, hsCRP, leptin and adiponectin information at 11 y. C-DII trajectories were estimated using latent class linear mixed models. We used linear mixed models for adiposity and logistic and multinomial regression for biomarkers. In girls, each one-point increase in C-DII score was associated with greater adiposity (abdominal-circumference 0.41%, p = 0.03; skinfold-sum 1.76%, p = 0.01; and BMI Z-score 0.05, p = 0.01). At 11 y the C-DII was associated with greater leptin (34% ≥ 13.0 ng/mL, p = 0.03) and hsCRP concentrations (29% ≥ 3.00 mg/L, p = 0.06) and lower adiponectin/leptin ratio (75% < 2.45, p = 0.02). C-DII trajectory 3 in boys was associated with a 75.2% (p < 0.01) increase in leptin concentrations and a 37.9% decrease (p = 0.02) in the adiponectin/leptin ratio. This study suggests that the inflammatory potential of diet may influence adiposity in girls and the homeostasis of adipose tissue and chronic subclinical inflammation in 11-year-old children.

Early-Life Dietary Cadmium Exposure and Kidney Function in 9-Year-Old Children from the PROGRESS Cohort.

Cadmium (Cd) is a toxic metal associated with adverse health effects, including kidney injury or disease. The aims of this study were to estimate dietary Cd exposure during childhood, and to evaluate the association of early-life dietary Cd with biomarkers of glomerular kidney function in 9-year-old Mexican children. Our study included 601 children from the Programming Research in Obesity, Growth, Environment and Social Stressors (PROGRESS) cohort with up to five follow-up food frequency questionnaires from 1 to 9 years of age; and 480 children with measures of serum creatinine, cystatin C, and blood nitrogen urea (BUN), as well as 9-year-old estimated glomerular filtration rate. Dietary Cd was estimated through food composition tables. Multiple linear regression models were used to analyze the association between 1 and 9 years, cumulative dietary Cd, and each kidney parameter. Dietary Cd exposure increased with age and exceeded the tolerable weekly intake (TWI = 2.5 µg/kg body weight) by 16-64% at all ages. Early-life dietary Cd exposure was above the TWI and we observed inverse associations between dietary Cd exposure and kidney function parameters. Additional studies are needed to assess kidney function trajectories through adolescence. Identifying preventable risk factors including environmental exposures in early life can contribute to decreasing the incidence of adult kidney disease.

Higher dietary magnesium intake is associated with lower body mass index, waist circumference and serum glucose in Mexican adults.

BACKGROUND: Obesity and diabetes mellitus (DM) are public health concerns in Mexico of top-level priority due to their high prevalence and their growth rate in recent decades. The accumulation of adipose tissue leads to an unbalanced release of pro-oxidant factors, which causes cellular damage and favors the development of comorbidities. Recent evidence suggests that oxidative stress also promotes the accumulation of adipose tissue and the development of insulin resistance. The objective of this study is to evaluate the association between usual intake of antioxidant nutrients, specifically vitamins A, C, E and magnesium with body mass index (BMI), waist circumference (WC) and serum glucose concentrations in a representative sample of Mexican adults. METHODOLOGY: We analyzed data on diet, BMI, WC and serum glucose from the Mexican National Health and Nutrition Survey 2012. Analysis included 20- to 65-year-old adults without a known diagnosis of DM (n = 1573). Dietary information was obtained using the five-step multiple-pass method developed by the United States Department of Agriculture and adapted to the Mexican context. Nutrient usual intake distributions were estimated using the Iowa State University method, through the "Software for Intake Distribution Estimation" (PC-Side) v.1.02. Associations were analyzed using multivariate regression models. RESULTS: Higher dietary magnesium intake was associated with lower markers of adiposity, so that an increase in 10 mg per 1000 kcal/day of magnesium was associated with an average decrease in BMI of 0.72% (95% CI: -1.36, - 0.08) and 0.49 cm (95% CI: -0.92, - 0.07) of WC. Additionally, in women with normal glucose concentrations, an increase in magnesium intake was associated with an average decrease in serum glucose by 0.59% (95% CI: -1.08, - 0.09). CONCLUSION: The results suggest that magnesium intake is associated with lower BMI, WC and serum glucose in Mexican population. However, more studies are required to elucidate the nature of this association.

[Taste perception as a risk factor for childhood obesity]. / Percepción del gusto como factor de riesgo para obesidad infantil.

OBJECTIVE: Describir el papel de la percepción del gusto como factor de riesgo para el desarrollo de obesidad en niños. MATERIALS AND METHODS: ulos científicos publicados en PubMed entre el 1 de enero de 2011 y el 20 de marzo de 2016 para el tema sobrepeso y obesidad en niños de entre 0 y 12 años. Los algoritmos utilizados fueron (Obesity OR Overweight) AND Taste perception, Satiation, Satiety response, Appetite, Appetite regulation, Habituation, Taste receptors [MeSH] y PROP phenotype. En búsquedas subsecuentes se incluyeron artículos previos y posteriores a la fecha de la búsqueda general (hasta mayo 2018). RESULTS: Las preferencias por los sabores inician desde la gestación, por lo que los niños que son expuestos a sabores dulces en etapas tempranas de la infancia aumentan su riesgo de habituación a éstos. Asimismo, las experiencias hedónicas dadas por la ingestión de alimentos y bebidas dulces refuerzan el consumo de estos alimentos, lo que propicia la selección de productos o bebidas de sabor dulce en etapas posteriores. Estas preferencias se han asociado con el desarrollo de obesidad en los niños. Las variantes genéticas relacionadas con la percepción del gusto también pueden contribuir a la selección de cierto tipo de alimentos. Sin embargo, su relación con una mayor ingestión de energía, así como con un mayor peso corporal, ha sido poco explorada y ha mostrado resultados inconsistentes. CONCLUSIONS: Se requiere más evidencia para entender las interacciones ambientales y genéticas de la percepción del gusto, a fin de considerarlo un factor más en las intervenciones de política pública.

Percepción del gusto como factor de riesgo para obesidad infantil / Taste perception as a risk factor for childhood obesity

Resumen Objetivo Describir el papel de la percepción del gusto como factor de riesgo para el desarrollo de obesidad en niños. Material y métodos Se realizó una búsqueda inicial de artículos científicos publicados en PubMed entre el 1 de enero de 2011 y el 20 de marzo de 2016 para el tema sobrepeso y obesidad en niños de entre 0 y 12 años. Los algoritmos utilizados fueron (Obesity OR Overweight) AND Taste perception, Satiation, Satiety response, Appetite, Appetite regulation, Habituation, Taste receptors [MeSH] y PROP phenotype. En búsquedas subsecuentes se incluyeron artículos previos y posteriores a la fecha de la búsqueda general (hasta mayo 2018). Resultados Las preferencias por los sabores inician desde la gestación, por lo que los niños que son expuestos a sabores dulces en etapas tempranas de la infancia aumentan su riesgo de habituación a éstos. Asimismo, las experiencias hedónicas dadas por la ingestión de alimentos y bebidas dulces refuerzan el consumo de estos alimentos, lo que propicia la selección de productos o bebidas de sabor dulce en etapas posteriores. Estas preferencias se han asociado con el desarrollo de obesidad en los niños. Las variantes genéticas relacionadas con la percepción del gusto también pueden contribuir a la selección de cierto tipo de alimentos. Sin embargo, su relación con una mayor ingestión de energía, así como con un mayor peso corporal, ha sido poco explorada y ha mostrado resultados inconsistentes. Conclusiones Se requiere más evidencia para entender las interacciones ambientales y genéticas de la percepción del gusto, a fin de considerarlo un factor más en las intervenciones de política pública.

Abstract Objective To describe the role of taste perception in the development of sweet taste habituation as well as its relationship to the development of obesity in children. Materials and methods An initial search of scientific articles published in PubMed between January 1st, 2011 and March 20th, 2016 was performed in children between 0 and 12 years old. The algorithms used were (Obesity OR Overweight) AND (Taste perception, Satiation, Satiety response, Appetite, Appetite regulation Habituation, Taste receptors [MeSH]) and PROP phenotype. Subsequent searches included papers published before and after date of initial search (until May 2018). Results Flavor preferences start as early as taste system development during pregnancy. Therefore, children who are exposed to sweet flavors in early childhood, increase their risk of habituation to them. Likewise, the hedonic experiences given by the ingestion of sweet foods and beverages, reinforce the consumption of these foods, perpetuating their selection in later stages. Preference for sweet taste has been associated with the development of obesity in children. Functional genetic variants related to taste perception can also contribute to the selection of certain types of foods and there is enough evidence that supports this idea. However, its contribution to a higher energy intake as well as a higher body weight has been poorly explored with inconsistent results. Conclusions More evidence is required to understand the environmental and genetic interactions of taste perception, so in turn, it can be consider as a key factor for preventing child obesity.

Desarrollo de la capacidad para la regulación en salud en México.

La Academia Nacional de Medicina es un espacio esencial para discutir la ciencia de la regulación en salud y posicionar su impacto en la salud y la economía. Enmarcada dentro de la función rectora de la autoridad sanitaria, la regulación en salud es la acción de proteger a la población de los peligros sanitarios involuntarios contra los cuales el individuo no puede protegerse; es una función esencial de la salud pública, componente institucional del sistema de salud y, por ende, vinculada a sus reformas y a la cobertura universal. La regulación tiene sustento en un cuerpo teórico epidemiológico, organizacional, legal, sociológico y económico. Tiene un cuerpo metodológico que sustenta su proceso en el análisis de riesgos y se traduce en normas, implementaciones, cumplimiento, monitoreo y evaluación de la regulación. Tiene una arquitectura profesional, financiera, organizacional, legal y de gobernanza. Dada su acción universal tiene un impacto generalizado en la población y un sustancial efecto económico, influyendo en al menos 17 % del comercio internacional regional. La salud a través de sus autoridades regulatorias debe ser parte del dialogo comercial internacional.The National Academy of Medicine is an essential space to discuss regulatory science in health, and to position its impact on health and economy. Framed within the stewardship role of the health authority, health regulation is the action of protecting the population against involuntary health hazards against which the individual cannot protect him/herself. It is an essential function of public health, an institutional component of the health system and, therefore, linked to its reforms and to universal coverage. Regulation has its support on an epidemiological, organizational, legal, sociological and economic theoretical body. It has a methodological body that supports its regulatory process based on risk analysis and that is translated into regulations, implementations, compliance, monitoring and evaluation of the regulation. It has a professional, financial, organizational, legal and governance architecture. Given its universal action, it has a widespread impact on the population and a substantial economic effect, influencing on at least 17% of regional international trade. Health through its regulatory authorities should be an early part of international trade discussions.

Intakes of Energy and Discretionary Food in Mexico Are Associated with the Context of Eating: Mealtime, Activity, and Place.

BACKGROUND: The prevalence of obesity and the intake of discretionary foods [high saturated fat and/or added sugar (HSFAS) products and sugar-sweetened beverages (SSBs)] are high in Mexico. It is important to understand whether the intakes of HSFAS products and SSBs are associated with the context in which they are consumed. OBJECTIVE: Our aim was to estimate the associations between total energy and discretionary food (HSFAS products and SSBs) intakes and the context of eating (mealtime, activity, and place). METHODS: We used data from 10,087 participants aged ≥1 y from the Mexican National Health and Nutrition Survey 2012. Dietary intake was estimated through a 24-h dietary recall that included questions on mealtime, activity, and place in which each food item was consumed. The associations between energy and discretionary food intakes and the context of eating were estimated by using multiple linear regression stratified by age group and adjusted for sociodemographic variables. RESULTS: Compared with breakfast, the percentage of energy that HSFAS products contributed was 16-29 (range in all age groups) percentage points higher during midafternoon snacks and 16-23 percentage points lower at lunch and almuerzo (Mexican brunch); the percentage of energy from SSBs was 3.4-7.6 percentage points higher during midmorning snacks (P < 0.05). In many age groups and mealtimes, we found that compared with eating only while seated, the percentage of energy as HSFAS was 5.3-14 percentage points higher when watching television (P < 0.05). Compared with eating at home, the percentage of energy from HSFAS was 12-26 percentage points higher on the street and the percentage of energy from SSBs was 3.4-6.0 percentage points higher at school and 2.9-15 percentage points higher at work (P < 0.05). CONCLUSIONS: These results highlight the need to promote healthier food selection among the Mexican population when snacking and watching television and healthier food environments at work, school, and on the street.

The succinate receptor as a novel therapeutic target for oxidative and metabolic stress-related conditions.

The succinate receptor (also known as GPR91) is a G protein-coupled receptor that is closely related to the family of P2Y purinoreceptors. It is expressed in a variety of tissues, including blood cells, adipose tissue, the liver, retina, and kidney. In these tissues, this receptor and its ligand succinate have recently emerged as novel mediators in local stress situations, including ischemia, hypoxia, toxicity, and hyperglycemia. Amongst others, the succinate receptor is involved in recruitment of immune cells to transplanted tissues. Moreover, it was shown to play a key role in the development of diabetic retinopathy. However, most prominently, the role of locally increased succinate levels and succinate receptor activation in the kidney, stimulating the systemic and local renin-angiotensin system, starts to unfold: the succinate receptor is a key mediator in the development of hypertension and possibly fibrosis in diabetes mellitus and metabolic syndrome. This makes the succinate receptor a promising drug target to counteract or prevent cardiovascular and fibrotic defects in these expanding disorders. Recent development of SUCNR1-specific antagonists opens novel possibilities for research in models for these disorders and may eventually provide novel opportunities for the treatment of patients.

Placental gene expression of calcitonin gene-related peptide and nitric oxide synthases in preeclampsia: effects of magnesium sulfate.

OBJECTIVE: To determine placental gene expression of calcitonin gene-related peptide (CGRP), calcitonin receptor-like receptor (CRLR), receptor activity modifying protein 1 (RAMP1), and endothelial and inducible nitric oxide synthases (eNOS and iNOS) in mild preeclampsia, and to assess the effects of magnesium sulfate (MgSO4). METHODS: Term placentas were obtained from 10 normotensive (NT group), 10 preeclamptic (PE) patients treated with 0.9% NaCl solution (PES group), and 8 PE women who received MgSO4 (PEMgSO4 group). The levels of mRNA were evaluated by real-time PCR. RESULTS: Placental gene expression of CRLR, RAMP1 and iNOS were significantly higher (p < 0.001) in the PES group than in the NT group, without changes in CGRP. In addition, eNOS expression was 67% lower (p < 0.001) in the PES group. When compared with the PES group, the PEMgSO4 group showed significantly higher expression (p < 0.05) of CGRP, CRLR and eNOS, while iNOS was significantly lower (p < 0.05). CONCLUSION: Placental gene expression of CRLR, RAMP1 and iNOS is higher in preeclampsia than in normal pregnancy, and MgSO4 treatment increased CGRP and CRLR and presented opposite effects upon eNOS and iNOS.

[Functional significance of heat shock protein 90]. / Significado funcional de las proteínas de choque térmico de 90 kDa.

The heat shock protein 90 kDalpha (Hsp90) subfamily is constituted by five isoforms, among them Hsp90alpha and Hsp90beta are the more abundant cytosolic proteins. These two proteins are molecular chaperons that participate in numerous cellular processes, through interacting with more than 100 proteins known as client proteins of Hsp90. These client proteins include: transcriptional factors, kinase proteins and other proteins that participate in transcriptional and transductional regulation such as steroid hormone receptors and nitric oxide synthases. This review offers a retrospective in the recent information about molecular and cellular functions of Hsp90 in the vascular physiology. In addition, the studies that evaluate Hsp90 role in the renal physiology and pathophysiology are discussed. Finally, the molecular tools developed to manipulate the Hsp90 expression in vitro and in vivo, through its inhibition or over-expression are reviewed. All these studies together have allowed increasing our knowledge regarding the role of Hsp90 during normal and pathophysiological conditions.

Effects of magnesium sulphate on placental expression of endothelin 1 and its receptors in preeclampsia.

OBJECTIVES: To investigate the effects of magnesium sulphate (MgSO(4)) on placental expression of endothelin 1 (ET-1) and its receptors in preeclampsia (PE). DESIGN AND METHODS: Placentas were obtained from 10 normotensive (NT group) and 18 moderate preeclamptic (PE group) women. Among the PE group, 10 patients were treated with 0.9% NaCl solution (PES) and 8 women received MgSO(4) (PEMgSO(4)). Placental mRNAs of ET-1, ET-1(A) receptor (ET-1(A)R) and ET-1(B) receptor (ET-1(B)R) were evaluated by Northern blot and quantified using densitometry. RESULTS: Placental ET-1(B)R expression was lower (P<0.05) in the PES group without significant changes in the mRNAs of ET-1 and ET-1(A)R when compared with the NT group. MgSO(4) treatment was associated with decreased ET-1 and increased ET-1(B)R (P<0.05) expression, without significant changes in ET-1(A)R. CONCLUSIONS: The results of the present study showed that moderate PE is associated with low placental expression of ET-1(B)R, and MgSO(4) treatment resulted in placental expression changes of the ET-1/receptors system.

[Endothelin 1 and angiotensin II in preeeclampsia]. / Acciones de endotelina 1 y angiotensina II en embarazos complicados con preeclampsia.

INTRODUCTION: It is generally thought that development of hypertension in preeclampsia (PE) is due to generalized endothelial dysfunction and/or results from an imbalance in the production and/or action of vasoactive factors, resulting in higher cytosolic Ca2+ concentration which in turn leads to vasoconstriction and decreased blood pressure perfusion in organs, including the fetoplacental unit. Among vasoactive factors involved in blood pressure regulation, endothelin 1 (ET-1) and angiotensin II (Ang II) regulate cytosolic Ca2+ concentrations and therefore are considered in this review. PE is associated with higher circulating and placental ET-1 levels, observation that explains, at least in part, vasoconstriction and oxidative stress. Higher and lower Ang II sensitivity seen in PE and normal pregnancy, respectively, could not be explained by changes in renin-angiotensin system components, including Ang II receptors (AT1). During normal pregnancy, AT1 receptors are found as monomers and are inactivated by reactive oxygen species (ROS) leading to lower Ang II sensitivity. In contrast, PE is associated with increased AT1/bradykinin receptors (B2) heterodimers which are resistant to inactivation by ROS, maintaining increased AT1-receptor stimulated signaling in PE. In addition, AT-1 agonistic antibodies (AT1-AA) obtained from PE women increases intracellular Ca2+, NADPH oxidase components and ROS, effects not observed with normal pregnancy AT1-AA. CONCLUSION: High ET-1 levels, the presence of AT1/B2 receptor heterodimers and increased AT1-AA are involved, at least in part, in the hypertensive and oxidative stress states in PE.

Acciones de endotelina 1 y angiotensina II en embarazos complicados con preeclampsia / Endothelin 1 and angiotensin II in preeeclampsia

Introduction. It is generally thought that development of hypertension in preeclampsia (PE) is due to generalized endothelial dysfunction and/or results from an imbalance in the production and/or action of vasoactive factors, resulting in higher citosolic Ca2+ concentration which in turn leads to vasoconstriction and decreased blood pressure perfusion in organs, including the fetoplacental unit. Among vasoactive factors involved in blood pressure regulation, endothelin 1 (ET-1) and angiotensin II (Ang II) regulate citosolic Ca2+ concentrations and therefore are considered in this review. PE is associated with higher circulating and placental ET-1 levels, observation that explains, at least in part, vasoconstriction and oxidative stress. Higher and lower Ang II sensitivity seen in PE and normal pregnancy, respectively, could not be explained by changes in renin-angiotensin system components, including Ang II receptors (ATI). During normal pregnancy, ATI receptors are found as monomers and are inactivated by reactive oxygen species (ROS) leading to lower Ang II sensitivity. In contrast, PE is associated with increased ATl/bradicinin receptors (B2) heterodimers which are resistant to inactivation by ROS, maintaining increased ATI-receptor stimulated signaling in PE. In adittion, AT-1 agonistic antibodies (AT1-AA) obtained from PE women increases intracellular Ca2+, NADPH oxidase components and ROS, effects not observed with normal pregnancy AT1-AA. Conclusion. High ET-1 levels, the presence of AT1/B2 receptor heterodimers and increased AT1-AA are involved, at least in part, in the hypertensive and oxidative stress states in PE.

Introducción. Se reconoce que el desarrollo de la hipertensión en la preeclampsia (PE) resulta del daño endotelial generalizado y/o de la falta de equilibrio en la producción y/o acción de agentes vasoactivos, lo que conlleva al incremento en la concentración citosólica de Ca2+ que resulta en vasoconstricción y disminución de la perfusión sanguínea en los órganos, incluyendo la unidad fetoplacentaria. Dentro de los factores vaso-activos que regulan la presión arterial, en la presente revisión se consideró a la endotelina 1 (ET-1) y a la angiotensina II (Ang II), factores que regulan la concentración citosólica de Ca2+. En comparación con el embarazo normal, la PE se asocia con mayor concentración en suero y placenta de ET-1, lo que explica en parte la vasoconstricción y el estado de estrés oxidativo. La respuesta exagerada en la PE y el estado de refractariedad en el embarazo normal a la Ang II no pueden explicarse por componentes del sistema renina-angiotensina, incluyendo a los receptores de Ang II (ATI). Durante el embarazo normal los receptores AT-1 se encuentran en forma de monómeros y son inactivados por las especies reactivas de oxígeno (ROS), lo que se asocia con menor respuesta a Ang II. En cambio, la respuesta exagerada a la Ang II durante la PE puede deberse a la heterodimerizacion de los receptores ATI con los de bradicinina (B2), estado que les confiere resistencia a la inactivación por las especies reactivas de oxígeno (ROS), lo que explica el incremento en la concentración del Ca2+ intracelular. Además, los anticuerpos agonistas del receptor ATI (AT1-AA) de mujeres PE aumenta la concentración de Ca2+ intracelular, de la NADPH oxidasa y de ROS, efectos que no se presentan al utilizar AT1-AA de embarazadas normotensas. Conclusión. Las altas concentraciones de ET-1, la presencia de receptores ATI en forma de heterodimeros ATI/ B2 y el aumento en los AT1-AA explican en parte, el estado de hipertensión y de estrés oxidativo de la PE.

Decreased fractional urinary calcium excretion and serum 1,25-dihydroxyvitamin D and IGF-I levels in preeclampsia.

During preeclampsia several alterations of calcium metabolism have been described, the most common of them is hypocalciuria, which pathophysiology is still unclear. In order to assess the contribution of calciotropic hormones to urinary calcium excretion, a cross-sectional study was done including 26 preeclamptic Mexican women (PE group) and 26 normotensive control pregnant women (NT group). Total and fractional urinary calcium excretion were significantly lower (P<0.0001) in the PE group than in the NT group (82+/-7 versus 171+/-7 mg/24h and 0.62+/-0.38 versus 1.38+/-0.71%, respectively), without significant differences in creatinine clearance, urinary sodium excretion and phosphate tubular reabsorption. In addition, serum 1,25-(OH)(2)D and IGF-I levels were significantly (P<0.05) lower in the PE than in NT group (43+/-9 versus 50+/-9 pg/mL and 195+/-67 versus 293+/-105 ng/mL, respectively), without significant differences in serum PTH levels. In the NT group, association analysis showed that total and fractional urinary calcium excretions positively correlated with serum levels of 1,25-(OH)(2)D (P<0.01) and IGF-I (P<0.001). In the PE group, total urinary calcium excretion positively correlated only with serum 1,25-(OH)(2)D (P<0.05). In conclusion, the results obtained in this study confirm that PE is associated with hypocalciuria and suggest that 1,25-(OH)(2)D and/or IGF-I may be involved in the regulation of urinary calcium excretion.

Effects of magnesium sulfate on lipid peroxidation and blood pressure regulators in preeclampsia.

OBJECTIVES: To investigate the status of lipid peroxidation and serum levels of several vasoactive substances in preeclamptic (PE) pregnant women before and during treatment with magnesium sulfate (MgSO(4)). DESIGN AND METHODS: The study population included 16 PE women. Circulating levels of malondialdehyde (MDA), endothelin 1 (ET-1), nitric oxide (NO) metabolites, and calcitonin gene-related peptide (CGRP) were measured before (at admission) and during MgSO(4) treatment (at delivery and 24 h postpartum). RESULTS: At admission systolic and diastolic blood pressures were 157 +/- 3 mm Hg and 106 +/- 2 mm Hg, respectively, and decreased significantly during treatment at delivery and 24 h postpartum (P < 0.0001). Before treatment, serum MDA concentrations were 0.383 +/- 0.037 micromol/L, and decreased significantly during MgSO(4) administration at delivery and 24 h postpartum (P < 0.0001). In contrast, serum ET-1 levels at 24 h postpartum were significantly higher as compared with those observed before treatment (79 +/- 3 versus 65 +/- 2 pg/mL, P = 0.002). Serum NO metabolite concentrations were 26 +/- 3 micromol/L, and no significant changes were observed during treatment. Serum levels of CGRP were 50 +/- 3 pg/mL at admission, and increased significantly at partum (P < 0.001). Serum ET-1 correlated negatively with NO metabolites before treatment (r = -0.69, P = 0.002), but not during treatment. In contrast, ET-1 correlated positively with serum CGRP levels during treatment (r = 0.73, P = 0.002 and r = 0.71, P = 0.002, at delivery and 24 h postpartum, respectively), but not before treatment. CONCLUSIONS: This study demonstrates that MgSO(4) administration to PE pregnant women induced significant changes in lipid peroxidation, production of ET-1 and CGRP.