Phthalates are chemical compounds used as plasticizers to increase flexibility and elasticity of rigid polymers and as non-plasticizers as solvents and additives in cosmetics and personal care products. These compounds have low water solubility and since they are not covalently bound to the polymer they are easily released into the environment and absorbed by the human body. Afterwards, phthalates are rapidly metabolized into their respective monoesters being already detected in different biological samples, including blood, urine, saliva, amniotic fluid, umbilical cord blood and breast milk. In addition, phthalates can disrupt the endocrine system by binding to molecular targets and interfering with hormonal homeostasis, thus being classified as endocrine-disrupting compounds (EDCs). Due to these properties and their adverse effects, phthalates were classified as priority environmental pollutants by the United States Environmental Protection Agency (US EPA). Alongside this increase in exposure to phthalates, the incidence of cardiovascular diseases (CVD) has also increased over the years, with the occurrence of hypertensive disorders in pregnancy (HDP) being one of the main causes of maternal and foetal morbidity and mortality. There are several risk factors that influence the development of HDP, including exposure to EDCs, but the mechanisms involved are not yet known. Several studies have also suggested an association with phthalates, in rats they seem to promote changes in the vascular function, to affect the expression of proteins involved in cardiac function, to contribute to increased blood pressure, changes in lipid metabolism, and atherosclerosis. Thus, the aim of this thesis was to investigate how phthalates’ exposure affects the cardiovascular health, focusing on HDP. For that, studies were carried out on rat aorta and the human umbilical artery to evaluate the effects of di(2-ethylhexyl) phthalate (DEHP) and diethyl phthalate (DEP) in the vascular function. In the first study, rat aorta devoid of endothelium was contracted with noradrenaline and potassium chloride (KCl) and then subjected to different concentrations of DEHP (0.001-100 μM) to assess the vascular reactivity. Besides, since Ca2+ levels are the main determinant of contraction and relaxation, DEHP effects on Ca2+ currents were also analysed using the A7r5 cells. The data obtained showed that DEHP caused a concentration-dependent vasorelaxation after contraction with KCl, and, at the highest concentrations, it inhibited both the basal and the BAY K8644-stimulated calcium currents. These results suggest that DEHP induces vasorelaxation of the rat aorta by inhibiting the L-type Ca2+ channels (LTCC). Then, the genomic and non-genomic effects of DEP on the rat aorta were analysed. Using the organ bath technique, DEP (0.001-1000 μM) was analysed after contraction of the arteries with noradrenaline and KCl. Similarly, to understand the possible mechanisms involved, the effects of DEP were analysed on the relaxing effect of nifedipine (NIF - specific calcium channel blocker) and sodium nitroprusside (SNP - soluble guanylate cyclase activator). Besides, through electrophysiology studies the non-genomic (occurring within a few minutes) and genomic (occurring after 24h of exposure) effects of DEP on the Ca2+ currents of the A7r5 cells were investigated. These showed that both the rapid and 24h effects of DEP exposure led to a decrease in LTCC currents, being in agreement with the vasorelaxation obtained through the organ bath experiments. For the first time, the vascular electrophysiological properties of an EDC were analysed after long-term exposure, concluding that DEP promotes an inhibition of the calcium current in the rat aorta, which may be responsible for electrical disturbances such as arrhythmias. To evaluate the effect of phthalates on maternal health, the last experimental work of this thesis analysed the contribution of DEP (0.001-1000 μM) in the development of gestational hypertension. Therefore, human umbilical arteries (HUA) were collected from normotensive and hypertensive pregnant women. To assess the non-genomic vascular effects, the HUA were pre-contracted with serotonin, histamine and KCl and then subjected to DEP, resulting in a vasorelaxation by interfering with Ca2+ channels and serotonin and histamine receptors. On the other hand, to assess the genomic effects, the arteries were incubated with DEP for 24h, and then the effects of NIF and SNP were analysed. The results showed that DEP seemed to act through the NO/sGC/cGMP/PKG signalling pathway, and to interfere with LTCC. In addition, primary culture of HUA smooth muscle cells was also performed for cell viability essays, showing that DEP has no toxic effect on these cells. Overall, this experimental work showed that DEP affects the HUA vascular resistance through disturbances in hormone and calcium homeostasis, suggesting that the development of hypertension in pregnancy may be a consequence of exposure to phthalates. In general, the results obtained show that phthalates modify the vascular homeostasis in both animals and humans, promoting vasorelaxation mainly through the inhibition of Ca2+ channels. This is the first time that an experimental study has been able to establish the link between exposure to DEP and gestational hypertension. We are beginning to unravel the mechanistic pathways involved in the vascular effects of phthalates that explain the pathological functional alterations of hypertension in pregnancy. However, more experimental studies are needed to understand how different classes and mixtures of phthalates affect the cardiovascular health during pregnancy and in future generations.

Testosterone (T) is the predominant endogenous androgen in the bloodstream. At the vascular level, T presents genomic and non-genomic effects, and both effects may overlap. The genomic actions assume that androgens can freely cross the plasma membrane of target cells and bind to nuclear androgen receptors, inducing gene transcription and protein synthesis. The non-genomic effects have a more rapid onset and may be related to the interaction with protein/receptor/ion channels of the plasma membrane. The key T effect at the vascular level is vasorelaxation, which is primarily due to its rapid effect. Thus, the main purpose of this review is to discuss the T non-genomic effects at the vascular level and the molecular pathways involved in its vasodilator effect observed in in vivo and in vitro studies. In this sense, the nuclear receptor activation, the influence of vascular endothelium and the activation or inhibition of ion channels (potassium and calcium channels, respectively) will be reviewed regarding all the data that corroborated or not. Moreover, this review also provides a brief update on the association of T with the risk factors for cardiovascular diseases, namely metabolic syndrome, type 2 diabetes mellitus, obesity, atherosclerosis, dyslipidaemia, and hypertension. In summary, in this paper we consider the non-genomic vascular mode of action of androgen in physiological conditions and the main risk factors for cardiovascular diseases.

Cardiovascular diseases (CVD) are one of the leading causes of death worldwide. Testosterone (T) is an important sex hormone that triggers several genomic and non-genomic pathways, leading to improvements of several cardiovascular risk factors and quality of life in men. At the vascular level, the key effect of T is the vasorelaxation. This review discusses the molecular pathways and clinical implications of T in the vascular system. Firstly, the mechanisms involved in the T vasodilator effect will be presented. Then, it will be discussed the association of T with the main risks for CVD, namely metabolic syndrome, type 2 diabetes mellitus, obesity, atherosclerosis, dyslipidaemia and hypertension. Several studies have shown a correlation between low T levels and an increased prevalence of several CVD. These observations suggest that T has beneficial effects on the cardiovascular system and that testosterone replacement therapy may become a therapeutic reality for some of these disorders.

Ensaios clínicos demonstraram que o tratamento da hipertensão estágio 1 e 2 pode reduzir o risco de doenças cardiovasculares. Entretanto, apesar da disponibilidade de tratamento efetivo, mais da metade dos pacientes em tratamento de hipertensão abandonam completamente o tratamento em aproximadamente um ano após o diagnóstico. Assim, o uso Short Message Services (SMS) via telefone celular poderia representar um recurso simples, capaz de promover o uso regular dos medicamentos por parte dos pacientes, evitando agravamento de estado. O presente estudo foi conduzido como um ensaio clínico controlado randomizado, aberto, do tipo crossover, unicêntrico, com duração de 17 meses, e envolveu 57 sujeitos hipertensos recrutados em centros de saúde da Universidade do Estado do Rio de Janeiro. Os pacientes foram aleatoriamente distribuídos em grupos para receberem ou não mensagens de texto via telefone celular objetivando o desenvolvimento de comportamento condicionado e o aumento da aderência ao tratamento. Ao fim do estudo as medidas médias das pressões arteriais foram comparadas a fim de verificar-se o nível de controle de cada grupo. Nos resultados não foram observadas diferenças significativas pela utilização do serviço de mensagens, mas identificou-se que ambos os grupos foram capazes manter o controle médio da pressão arterial, independente do reforço oferecido via SMS.

Modifications in contemporary lifestyles reflect negatively on the individuals’ health status and are associated with the incidence of cardiovascular risk factors (CVRF), and hence with the genesis of cardiovascular disease (CVD). Currently, 31.3% of deaths in Brazil occur in consequence of CVD. It is observed that CVRF have been affecting the younger population, even the Brazilian military. Therefore, the aim of this study was to determine the prevalence of some CVRF in cadets from the Brazilian Air Force Academy (AFA). It was a cross-sectional observational study that evaluated 166 cadets from the 1st to the 4th year of the AFA. Data collection was performed at the AFA’s Clinic of Nutrition from the Health Subdivision , with measures of anthropometric data: weight, height, body mass index, waist circumference and skinfold thickness. Blood was collected for lipid profile and serum glucose evaluation. Blood pressure was measured at rest. Three-day food records were collected and analyzed using the software Avanutri®. Lifestyle was assessed with a questionnaire which included physical activity and smoking habit data. The Pearson Chi-Square or Fisher's exact tests were used to assess the associations between CVRF, gender and the year of entrance at the AFA. The food consumption data were adjusted to the energy by the residual method. The significance level of 5% was adopted as standard. The study was submitted to the Ethics Committee of Federal University of Goias and approved under Protocol n°. 189/12. The sample was composed of 147 men and 19 women, mean (± SD) age of 21.5 ± 1.2 and 21.6 ± 0.9 years, respectively. It was verified that 29.7% of men and 16.7% of women were overweight or obese. The prevalence of hypertension among men was 15.2%. The lipid profile revealed that 50.7% of the cadets had hypercholesterolemia, 24.3% had elevated LDL-c and 11.2%, low HDL-c. There was a significant association between the time spent at AFA and low HDL-c. The prevalence of low HDL-c was statistically higher among the cadets from the 1st and 2nd years. Food consumption data showed that 58.7% of men and 50% of women had an intake above the daily requirement. There was a high prevalence of saturated fats (87.2%) and cholesterol (42.7%) intake in both genders. No cadet reached the recommendations for monounsaturated and polyunsaturated fat intake and the inadequate intake of dietary fiber was reported in 92.7% of them. It was verified that the young military personnel are exposed to CVRF in a similar manner to young civilians. These results are relevant in order to create and install multidisciplinary approaches aiming at reducing the risk of CVD in the early stages of adulthood, thereby ensuring a better quality of life and reduction of cardiovascular health problems in the long term of the future officers of Brazilian Air Force.

To verify the relationship between the polymorphisms rs18011282 in PPAR-gamma gene and rs429358 + rs7412 in apolipoprotein E gene and lipid profile of adolescents under cardiovascular risk factors. Material and methods: The study sample was composed of 115 adolescents aged 10-19 years, which presented cardiovascular risk factors. The students were evaluated regarding socioeconomic, anthropometric, biochemical, genetic and dietetic variables. ANOVA or Kruskal-Wallis tests were used in the analysis of ungrouped genotypes, while Student’s t-test or Mann-Whitney test were applied to the analysis of the grouped genotypes. Results: The overweight adolescents presented lower HDL-c concentrations (p=0.0016). Those carrying PPAR-gamma Ala allele showed higher serum TAG (p=0.0423) and VLDL-c (p=0.0410) levels when compared to those carrying the Pro allele. For the apolipoprotein E gene polymorphism, it was observed a tendency of higher TAG (p=0.0712) and VLDL-c (p=0.0758) levels in the adolescents carrying the E4 allele when compared to those who did not carry this allele. Conclusion: The polymorphisms PPAR-gama rs18011282 and apolipoprotein E rs429358 + rs7412 seem to be related to the development of lipid profile alterations in adolescents.

Introduction: Cardiovascular risk factors (CRF) can begin in childhood subtly and last until adulthood, they may be present in an isolated or grouped form in the same individual, and thus increase cardiovascular risk. One of the most present CRF is obesity, especially abdominal obesity, which is strongly associated with metabolic dysfunction. Therefore, it is necessary instruments of easy access for the tracking of the cardiovascular risk in childhood. In the literature studies on CRF in children are still incipient and need to be better understood, especially in the state of Goiás. Objective: To analyze the cardiovascular risk factors grouped in preschool and school children in the city of Santo Antônio de Goiás. Method: An epidemiological study was carried out, with a cross-sectional study and a case-control study, in the city of Santo Antônio de Goiás, with students from 4 to 11 years of age enrolled in the public network. Anthropometric data (body mass index - BMI and waist circumference - WC), resting blood pressure (BP), fasting glycemia and lipid profile (high density lipoprotein HDL, low density lipoprotein LDL) were collected and evaluated, triglycerides - TG and total cholesterol - TC), besides the level of physical activity. Grouped CRFs were considered when the same individual had equal or more than 3 altered indicators. To verify the normality of the data, the Kolmogorov-Smirnov test was performed. Initially, data were analyzed for mean, standard deviation and frequency. The comparison of means between the groups was performed by Student's t-test for independent samples or Mann Whitney. The association between the variables (anthropometric, biochemical and hemodynamic) were evaluated by the Pearson's Chi-square test and correlation analysis between the absolute values of the variables indicative of the FRC was used the Spearman correlation, Regression analysis Binary Logistics to identify significant predictors for outcome: cardiovascular risk factors grouped and isolated. For all tests the significance level of 5% was adopted. Results: Of the 158 schoolchildren evaluated, 24.7% were overweight and 29.7% were abdominal adiposity. The prevalence of arterial hypertension was 11.4% and dyslipidemia 72.8%, only glycemia was identified within normal values for all children. The comparative analysis of CRF indicated association of BMI, MC and SBP in both preschoolers and schoolchildren with increased CD, in addition to higher PAD and TG values in students with increased CD. Positive and significant correlation was still found between CC values and SBP and DBP values for all children. In addition, the results of binary logistic regression showed that school-aged children with increased CD were 1.10 times more likely to present clustering risk factors. Conclusion: Dyslipidemia was the most prevalent CRF among preschoolers and schoolchildren, followed by abdominal adiposity and excess body weight. In the group of children evaluated, abdominal adiposity directly influenced blood pressure values in both groups and in triglyceride values in schoolchildren. CC was able to predict CRF in only the older group of children.