RESUMO
This work was designed to study the expression of the vasodilator peptide angiotensin-(1-7) [Ang-(1-7)] and its generating enzyme (ACE2) in the uteroplacental interface. Placentas were obtained from 11 early pregnancy failures (5 miscarriages and 6 ectopic pregnancies), 15 normotensive, and 10 preeclamptic gestations. In placental villi, the main sites of immunocytochemical expression of Ang-(1-7) and ACE2 were the syncytiotrophoblast, cytotrophoblast, endothelium and vascular smooth muscle of primary and secondary villi. Syncitial Ang-(1-7) expression in samples obtained from miscarriages and ectopic pregnancies was increased compared to normal term pregnancy [2.0 (2.0-2.25 for the 25 and 75% interquartile range) vs 1.3 (1.0-1.9), p<0.01]. In the maternal stroma, Ang-(1-7) and ACE2 were expressed in the invading and intravascular trophoblast and in decidual cells in all 3 groups. Ang-(1-7) and ACE2 staining was also found in arterial and venous endothelium and smooth muscle of the umbilical cord. The expression of Ang-(1-7) and ACE2 was similar in samples obtained from normal term or preeclamptic pregnancies, except for increased expression of ACE2 in umbilical arterial endothelium in preeclampsia [0.5 (0.5-0.8) vs 0.0 (0.0-0.0), p<0.01]. The uteroplacental location of Ang-(1-7) and ACE2 in pregnancy suggests an autocrine function of Ang-(1-7) in the vasoactive regulation that characterizes placentation and established pregnancy.
Assuntos
Angiotensina I/análise , Carboxipeptidases/análise , Fragmentos de Peptídeos/análise , Placenta/química , Complicações na Gravidez/metabolismo , Gravidez/metabolismo , Angiotensina I/metabolismo , Enzima de Conversão de Angiotensina 2 , Carboxipeptidases/metabolismo , Feminino , Humanos , Imuno-Histoquímica , Fragmentos de Peptídeos/metabolismo , Peptidil Dipeptidase A , Placenta/enzimologia , Placenta/metabolismo , Pré-Eclâmpsia/metabolismo , Complicações na Gravidez/enzimologiaRESUMO
BACKGROUND: Postmenopausia and hypercholesterolemia are related to endothelial dysfunction, a pathogenic event in atherosclerosis. Soy protein reduces plasma cholesterol, but there is scanty information about its effect on endothelial function. OBJECTIVE: To evaluate the effect of isolated soy protein compared to caseinate on plasma lipoproteins and endothelial function in postmenopausal hypercholesterolemic women. DESIGN: Randomized, double-blind, cross-over trial. SETTING: Outpatient clinic of the Catholic University of Chile. SUBJECTS: Eighteen healthy, postmenopausal women with hypercholesterolemia were recruited, included and completed the protocol. INTERVENTIONS: During the trial, all patients followed a low fat/low cholesterol diet and were randomly assigned to receive isolated soy protein or matching caseinate for 4 weeks, and then the alternative treatment until week 8. At pre-study and at the end of the first and second period, plasma lipoprotein levels and endothelial function (flow-mediated dilatation (FMD) of the brachial artery) were evaluated. RESULTS: Plasma total and low density lipoprotein (LDL)-cholesterol concentration were significantly lower with the low fat/low cholesterol diet compared to pre-study, either with caseinate or soy protein. No significant differences in plasma lipid concentration between caseinate or soy protein interventions were observed. FMD did not change with the caseinate. In contrast, when soy protein was administered, FMD was significantly higher compared to pre-study (9.4+/-1.8% vs 5.3+/-1.2%; P<0.05) and compared to caseinate intervention (9.4+/-1.8% vs 4.9+/-1.5%; P<0.033). CONCLUSIONS: These results suggest that in postmenopausal hypercholesterolemic women, soy protein improves endothelial function, regardless of changes in plasma lipoproteins.
Assuntos
Colesterol/sangue , Endotélio Vascular/efeitos dos fármacos , Hipercolesterolemia/dietoterapia , Proteínas de Soja/administração & dosagem , Idoso , Artéria Braquial/diagnóstico por imagem , Artéria Braquial/patologia , Caseínas/administração & dosagem , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Estudos Cross-Over , Método Duplo-Cego , Endotélio Vascular/fisiologia , Feminino , Humanos , Hipercolesterolemia/fisiopatologia , Pessoa de Meia-Idade , Pós-Menopausa , Proteínas de Soja/uso terapêutico , Ultrassonografia , Vasodilatação/efeitos dos fármacosRESUMO
Based on two patients, we discuss the difficulties in diagnosing and managing primary aldosteronism in pregnancy, which derive from changes of the renin-angiotensin-aldosterone axis, from the uncertainty regarding blood pressure control along gestation and postpartum, and from the contraindication to the use of spironolactone. The first case is a 27 years old woman with a long standing refractory hypertension, a hemorrhagic stroke with left brachial hemiplegia and crural hemiparesia, two miscarriages, one stillbirth and one offspring with intrauterine growth retardation. Due to hypokalemia, a plasma aldosterone/renin activity ratio of 91, and a negative genetic screening for glucocorticoid remediable aldosteronism (GRA), a primary hyperaldosteronism with normal adrenals in CT scan was diagnosed, and good blood pressure control was attained with spironolactone. After two and a half years of normotension, a fifth pregnancy, managed with methyldopa evolved with satisfactory blood pressures, plasma potassium, fetal growth, uterine and umbilical arterial resistance indexes, and maternal endothelial function. At 37 1/2 weeks of pregnancy the patient delivered a healthy newborn weighing 2,960 g. Blood pressure rose during the 48 hours of postpartum in the absence of proteinuria and required i.v. hydralazine. The second patient is a 37 years old woman, with known refractory hypertension for 7 years, hypokalemia, plasma aldosterone/renin activity ratio greater than 40, normal adrenals in the CAT scan, and a negative genetic screening for GRA. She had normotensive pregnancies 5 and 3 years prior to the detection of hypertension, with hypertensive crisis in both postpartum periods, retrospectively considered as expressions of primary hyperaldosteronism.
Assuntos
Humanos , Feminino , Gravidez , Adulto , Complicações na Gravidez/fisiopatologia , Hiperaldosteronismo/fisiopatologia , Complicações na Gravidez/diagnóstico , Complicações na Gravidez/tratamento farmacológico , Hiperaldosteronismo/diagnóstico , Hiperaldosteronismo/tratamento farmacológicoRESUMO
OBJECTIVES: Indirect evidence suggests that adrenal steroid production in the human fetus may have a circadian rhythm. To assess whether there is a 24-hour rhythm of fetal cortisol in the human fetus, we investigated the relationship between fetal and maternal cortisol and cortisone concentrations in maternal, umbilical arterial, and umbilical venous blood samples over a 24-hour period. STUDY DESIGN: Elective cesarean sections were scheduled every 2 hours around the clock in 57 term (38-41 weeks' gestation) nonlaboring pregnant women. Plasma cortisol and cortisone concentrations were measured by high-pressure liquid chromatography. RESULTS: The mean 24-hour cortisol concentration was higher in umbilical arterial than in umbilical venous blood samples, 63.6 +/- 4.6 ng/mL (SEM) versus 48.7 +/- 3.2 ng/mL, respectively (P <.05). Fetal plasma cortisol showed a rhythm in the umbilical artery (acme from noon to 4 PM ) (1-way analysis of variance and least significant difference test; P <.05) but not in the umbilical vein. Umbilical arteriovenous differences showed no net transfer of cortisol to the fetus at any time of the day and net fetal production of cortisol from 8 AM to 6 PM. There was limited transfer of cortisone to the fetus and only in the 2 AM -to-noon time interval. CONCLUSION: These data suggest the presence of a 24-hour rhythm of fetal adrenal cortisol secretion that may be controlled by a fetal circadian pacemaker.
Assuntos
Ritmo Circadiano , Parto Obstétrico , Sangue Fetal , Hidrocortisona/sangue , Adulto , Cromatografia Líquida de Alta Pressão , Cortisona/sangue , Feminino , Humanos , GravidezRESUMO
Since normal human pregnancy is characterized by normotension in the face of an increased renin-angiotensin-aldosterone system (RAAS), we evaluated the temporal pattern of urinary excretion of a novel vasodilator within this system, angiotensin-(1-7) (Ang-[1-7]), during the menstrual cycle, pregnancy, and lactation. The urinary profiles of Ang I, Ang II, human chorionic gonadotropin, 17beta-estradiol, and progesterone were also determined. During the menstrual cycle, urinary Ang-(1-7) and Ang II remained stable (mean cycle value: 94.6 +/- 11.3 and 11.4 +/- 1.1 pmol/g of creatinine, respectively) in nine females. In 10 normal pregnant women, urinary Ang-(1-7) and Ang II increased throughout gestation, averaging 1499.8 +/- 310 and 224.4 +/- 58 pmol/g of creatinine, respectively (p < 0.05) at wk 35 and falling during lactation to 394.0 +/- 95 and 65.7 +/- 20 pmol/ g of creatinine (p < 0.05), respectively. The Ang-(1-7)/Ang II ratio was unchanged in the different reproductive periods. During the menstrual cycle, Ang II and Ang-(1-7) correlated with 17beta-estradiol and progesterone using multivariate analysis (r = 0.31, p < 0.001) and r = 0.28, p < 0.02, respectively). During gestation, 17beta-estradiol and progesterone correlated with urinary Ang-(1-7) (r = 0.48, p < 0.001 and r = 0.47, p < 0.001, respectively) and Ang II (r = 0.24, p < 0.03 and r = 0.25, p < 0.03, respectively); by multiple regression, only Ang-(1-7) correlated with both steroids (r = 0.49,p < 0.001). The progressive rise of Ang-(1-7) throughout gestation, probably modulated by estrogen and progesterone, suggests a physiologic counterregulation within the RAAS.
Assuntos
Angiotensinas/fisiologia , Lactação/urina , Ciclo Menstrual/urina , Gravidez/urina , Vasoconstrição/fisiologia , Vasodilatação/fisiologia , Adulto , Angiotensina I/fisiologia , Angiotensina I/urina , Angiotensina II/fisiologia , Angiotensina II/urina , Angiotensinas/urina , Feminino , Humanos , Fragmentos de Peptídeos/fisiologia , Fragmentos de Peptídeos/urinaRESUMO
OBJECTIVE: To evaluate the relationship of Clara cell protein (CCP) in amniotic fluid (AF) with the lecithin/sphingomyelin (L/S) ratio, and the concentrations of saturated phosphatidylcholine (Sat PC) and surfactant protein A (SP-A). STUDY DESIGN: AF samples were obtained by amniocentesis from 98 pregnancies without conditions known to influence fetal lung maturation between 25 and 41 weeks of gestation. These samples were used for determinations of CCP, L/S ratio, Sat PC, and SP-A. Simple and multiple linear regressions were used to analyze the data. RESULTS: CCP in AF increased logarithmically with gestational age (R(2)=0.51, p=0.006). The L/S ratio (R(2)=0.41, p<0.001), and the concentrations of Sat PC (R(2)=0.26, p<0.001) and SP-A (R(2)=0.52, p<0.001) also increased with advancing gestation. Weak correlations of CCP with the L/S ratio (R(2)=0.22, p=0.009) and Sat PC (R(2)=0.12, p=0.004), but not with SP-A (R(2)=0.07, p=0.10), were found. Using multiple linear regressions, gestational age was the only predictor of CCP (F=10.9, R(2)=0.13, p=0.015). Conversely, gestational age, Sat PC, and SP-A accounted for most of the variation of the L/S ratio (F=34.7, R(2)=0.61, p=0.0001). CONCLUSION: CCP correlated very poorly with known and widely accepted indices of fetal lung maturation. The increasing concentration of CCP in AF throughout gestation probably reflects growth and development of the fetal airways.