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Activation of the angiotensin (Ang)-converting enzyme (ACE) 2/Ang-(1-7)/MAS receptor pathway of the renin-angiotensin system (RAS) induces protective mechanisms in different diseases. Herein, we describe the cardiovascular phenotype of a new transgenic rat line (TG7371) that expresses an Ang-(1-7)-producing fusion protein. The transgene-specific mRNA and the corresponding protein were shown to be present in all evaluated tissues of TG7371 with the highest expression in aorta and brain. Plasma Ang-(1-7) levels, measured by radioimmunoassay (RIA) were similar to control Sprague-Dawley (SD) rats, however high Ang-(1-7) levels were found in the hypothalamus. TG7371 showed lower baseline mean arterial pressure (MAP), assessed in conscious or anesthetized rats by telemetry or short-term recordings, associated with increased plasma atrial natriuretic peptide (ANP) and higher urinary sodium concentration. Moreover, evaluation of regional blood flow and hemodynamic parameters with fluorescent microspheres showed a significant increase in blood flow in different tissues (kidneys, mesentery, muscle, spleen, brown fat, heart and skin), with a resulting decrease in total peripheral resistance (TPR). TG7371 rats, on the other hand, also presented increased cardiac and global sympathetic tone, increased plasma vasopressin (AVP) levels and decreased free water clearance. Altogether, our data show that expression of an Ang-(1-7)-producing fusion protein induced a hypotensive phenotype due to widespread vasodilation and consequent fall in peripheral resistance. This phenotype was associated with an increase in ANP together with an increase in AVP and sympathetic drive, which did not fully compensate the lower blood pressure (BP). Here we present the hemodynamic impact of long-term increase in tissue expression of an Ang-(1-7)-fusion protein and provide a new tool to investigate this peptide in different pathophysiological conditions.
Assuntos
Angiotensina I/metabolismo , Sistema Cardiovascular/metabolismo , Hemodinâmica , Hipertensão/prevenção & controle , Fragmentos de Peptídeos/metabolismo , Sistema Nervoso Simpático/metabolismo , Angiotensina I/genética , Animais , Arginina Vasopressina/metabolismo , Fator Natriurético Atrial/metabolismo , Velocidade do Fluxo Sanguíneo , Pressão Sanguínea , Sistema Cardiovascular/fisiopatologia , Modelos Animais de Doenças , Genótipo , Proteína Glial Fibrilar Ácida/genética , Proteína Glial Fibrilar Ácida/metabolismo , Hemodinâmica/genética , Hipertensão/genética , Hipertensão/metabolismo , Hipertensão/fisiopatologia , Masculino , Fragmentos de Peptídeos/genética , Fenótipo , Ratos Sprague-Dawley , Ratos Transgênicos , Proteínas Recombinantes de Fusão/metabolismo , Fluxo Sanguíneo Regional , Sistema Nervoso Simpático/fisiopatologia , Fatores de Tempo , Resistência VascularRESUMO
(1) Background: The aim of this study was to assess associations between particulate matter (PM) exposure and natriuretic peptide concentrations in cord blood from newborns. (2) Methods: we conducted a cross-sectional study in Mexico City with 101 pregnant women from CIMIGEN Hospital. Atrial natriuretic peptide (ANP), B-type natriuretic peptide (BNP) and C-type natriuretic peptide (CNP) were measured in plasma from cord blood in 51 newborns by ELISA. We estimated PM exposure (PM2.5 and PM10) at first, second and third trimester of pregnancy. (3) Results: The median and interquartile range for ANP, BNP and CNP plasma concentrations were 66.71 (46.92-80.23), 98.23 (73.64-112.30) and 1129.11 (944.10-1452.02) pg/mL, respectively. PM2.5 and PM10 levels for the whole pregnancy period were 22.2 µg/m3 and 41.63 µg/m3, respectively. Employing multivariable linear regression models adjusted for maternal age, newborn sex, smoking before pregnancy, maternal occupation and newborns' length and height, we observed a 2.47 pg/mL (95%CI: -4.67, -0.27) decrease in BNP associated with PM2.5 exposure during second trimester. Adjusted for the same set of confounders, third trimester PM10 exposure was inversely associated with ANP concentrations (beta estimate: -0.90; 95% CI: -1.80, -0.03). Neither PM10 nor PM2.5 were associated with CNP at any trimester of pregnancy. (4) Conclusions: Prenatal exposure to particulate matter was associated with ANP and BNP decrease in newborns.
Assuntos
Poluição do Ar , Material Particulado , Fator Natriurético Atrial , Estudos Transversais , Feminino , Humanos , Recém-Nascido , Exposição Materna/efeitos adversos , México , Peptídeos Natriuréticos , Material Particulado/análise , GravidezRESUMO
Waste cooking oil (WCO) is a valuable feedstock for the synthesis of biodiesel but the product exhibits poor oxidative stability. Techniques available for assessing this parameter are generally expensive and time-consuming, hence the purpose of this study was to develop and validate a rapid and reliable predictive system based on signals from the sensors of a commercial hand-held e-nose instrument. Biodiesels were synthesized from soybean oil and six samples of WCO, and their physicochemical characteristics and oxidative stabilities determined before and after storage in different types of containers for 30 or 60 days at room temperature or 43 °C. Linear regression models were constructed based on principal component analysis of the signals generated by all 32 e-nose sensors and stochastic modeling of signal profiles from individual sensors. The regression model with principal components as predictors was unable to explain the oxidative stability of biodiesels, while the regression model with stochastic parameters (combining signals from 11 sensors) as predictors showed an excellent goodness of fit (R2 = 0.91) with a 45-sample training set and a good quality of prediction (R2 = 0.84) with a 18-sample validation set. The proposed e-nose system was shown to be accurate and efficient and could be used to advantage by producers/distributors of biodiesel in the assessment fuel quality.
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Compared with mammalian ANP32A, most avian-coded ANP32A contains a 33 amino acids insertion (ch-ANP32A-33) or a 29 amino acids insertion (ch-ANP32A-29), which can rescue the mammalian-restricted avian influenza virus polymerase activity, with ch-ANP32A-33 exhibiting a more potent phenotype. The alternative splicing of 3' splice sites (SSs) of chicken ANP32A intron 4 generates full-length ch-ANP32A-33 and truncated ch-ANP32A-29. In this study, we found a splicing regulatory cis-element that affected the alternative splicing of 3' SSs by block-scanning mutagenesis. RNA affinity purification and mass spectrometry showed that the SRSF10 bound to the splicing cis-element and the binding was further identified and confirmed by RIP experiment. Overexpression of SRSF10 changed the ratio of the two chicken ANP32A transcripts with the increased ch-ANP32A-29 and the decreased ch-ANP32A-33. The knockdown of both of the ch-ANP32A-33 and ch-ANP32A-29 was harmful to avian influenza virus polymerase activity in DF-1 cells, but the restoration and increasement of only ch-ANP32A-29 could not completely rescue the activity of avian influenza virus polymerase. Overexpression of SRSF10 negatively affected the polymerase activity and replication of avian influenza virus, and the expression of ch-ANP32A-33 could partially recover the decrease of polymerase activity of avian influenza virus. By contrast, SRSF10â¯had weak inhibition on the polymerase activity of mammalian adapted influenza virus and had no effect on the replication of mammalian adapted influenza virus. Taken together, we demonstrated that SRSF10 acts as a negative regulator in polymerase activity and replication of avian influenza virus by binding to the splicing cis-element to regulate the alternative splicing of chicken ANP32A intron 4 for the reduced ch-ANP32A-33 and increased ch-ANP32A-29.
Assuntos
Processamento Alternativo , Subtipo H7N9 do Vírus da Influenza A/fisiologia , Proteínas Nucleares/genética , Fatores de Processamento de Serina-Arginina/genética , Replicação Viral , Animais , Linhagem Celular , Galinhas/virologia , DNA Polimerase Dirigida por DNA/metabolismo , Regulação da Expressão Gênica , Subtipo H7N9 do Vírus da Influenza A/enzimologia , Subtipo H7N9 do Vírus da Influenza A/genética , Influenza Aviária/virologiaRESUMO
ABSTRACT For combustion engines to perform well, it is necessary that the fuel used be of high quality. Fuel quality can be analyzed through different physicochemical properties. This study presents comparisons between the values presented in literature, legislation and those obtained through experimental tests of different biodiesel samples. Biodiesel is a promising alternative of renewable energy obtained from raw material. The properties observed in this study are: Viscosity, density, cloud point, pour point and calorific value. The data explored by this work aims to bring solidification to the methodologies and equipment necessary for a better characterization of biodiesel.
Assuntos
Óleos de Plantas , Biocombustíveis , Energia Renovável , Gás NaturalRESUMO
BACKGROUND: The selective estrogen receptor modulators (SERMs) raloxifene and tamoxifen are used for the treatment of osteoporosis and cancer, respectively, in women. The impairment of both the Atrial Natriuretic Peptide (ANP) cell signaling system and the translocation of nuclear factor-kappa B (NF-kB) to the cell nucleus are associated with detrimental cardiovascular effects and inflammation. The effects of SERMs on these parameters in the cardiac tissue of estrogen-deficient rats has not been reported. METHODS: We investigated the effects of raloxifene and tamoxifen on ANP signaling, p65 NF-kB nuclear translocation, cardiac histology and contractility. Female rats were divided into five groups: control (SHAM), ovariectomized (OVX), OVX-treated 17-ß-estradiol (E), OVX-treated raloxifene (RLX) and OVX-treated tamoxifen (TAM). The treatments started 21days after ovariectomy and continued for 14days. RESULTS: Ovariectomy reduced ANP mRNA in the left atrium (LA), decreased the content of ANP protein in the LA and in plasma, and increased the level of p65 NF-kB nuclear translocation in the left ventricle. Both 17-ß-estradiol and SERMs were able to reverse these alterations, which were induced by the estrogen deficient state. The hemodynamic and cardiac structural parameters analyzed in the present work were not modified by the interventions. CONCLUSIONS: Our study demonstrates, for the first time, the additional benefits of raloxifene and tamoxifen in an estrogen-deficient state. These include the normalization of plasmatic and cardiac ANP levels and cardiac p65 NF-kB translocation. Therefore, these treatments promote cardiovascular protection and may contribute to the prevention of cardiac dysfunction observed long-term in postmenopausal women.
Assuntos
Fator Natriurético Atrial/metabolismo , Estrogênios/metabolismo , NF-kappa B/metabolismo , Cloridrato de Raloxifeno/farmacologia , Tamoxifeno/farmacologia , Transporte Ativo do Núcleo Celular/efeitos dos fármacos , Animais , Fator Natriurético Atrial/genética , Peso Corporal , Feminino , Coração , Hemodinâmica/efeitos dos fármacos , Miocárdio/metabolismo , Tamanho do Órgão/efeitos dos fármacos , Ovariectomia , Ratos , Moduladores Seletivos de Receptor Estrogênico/farmacologia , Útero/efeitos dos fármacosRESUMO
UNLABELLED: Anabolic-androgenic steroids are misused, including women, but little is known about the cardiovascular effects of these drugs on females. AIM: Evaluated the effects of nandrolone decanoate (ND), physical exercise and estrogen deficiency on female rats. MAIN METHODS: Female Wistar rats were divided into 8 groups: S and OVX: (SHAM: sham surgery; OVX: ovariectomy, vehicle), SE and OVXE (resistance exercise 5 times a week, vehicle), SD and OVXD (treated with ND, 20 mg/kg/week for 4 weeks); SDE and OVXDE. Treatments were initiated 21 days after surgery. The BezoldJarisch reflex was assessed by Phenylbiguanide administration. The right atrium, kidney, and serum were collected for molecular analyses by RT-PCR of atrial natriuretic peptide (ANP), A-type natriuretic peptide receptor (NPR-A) and NPR-C. ELISA assay to estradiol and testosterone concentrations. The gastrocnemius muscle, heart and kidney weights/tibia length were measured.Morphometric analysis of heart was made (H/E) and collagen content of heart and kidney were evaluated using Pirossirius Red. KEY FINDINGS: ND treatment increased ANP expression on atrium and decreased NPR-A expression in kidney. Physical exercise and ovariectomy did not alter this parameter. NPR-C level was reduced in the SDE and OVXDE. Renal and cardiac hypertrophy was observed after ND treatment, with collagen deposition. Plasma estrogen concentrations were reduced and serum testosterone concentrations were increased after ND treatment. SIGNIFICANCE: ANP has an important role in modulating the cardiovascular effects of ND in females. Thismodulating may have occurred by the increasing ANP expression, reducing NPR-A and NPR-C expression levels, and changing sex hormone levels.
Assuntos
Pressão Arterial/efeitos dos fármacos , Fator Natriurético Atrial/metabolismo , Frequência Cardíaca/efeitos dos fármacos , Coração/efeitos dos fármacos , Rim/efeitos dos fármacos , Nandrolona/análogos & derivados , Anabolizantes/farmacologia , Animais , Pressão Arterial/fisiologia , Barorreflexo/efeitos dos fármacos , Biguanidas/farmacologia , Colágeno/metabolismo , Estradiol/sangue , Estrogênios/deficiência , Feminino , Expressão Gênica/efeitos dos fármacos , Coração/anatomia & histologia , Átrios do Coração/efeitos dos fármacos , Átrios do Coração/metabolismo , Frequência Cardíaca/fisiologia , Hipertrofia , Rim/anatomia & histologia , Rim/metabolismo , Músculo Esquelético/anatomia & histologia , Miocárdio/metabolismo , Nandrolona/farmacologia , Decanoato de Nandrolona , Peptídeo Natriurético Tipo C/biossíntese , Tamanho do Órgão/efeitos dos fármacos , Ovariectomia , Condicionamento Físico Animal , Ratos , Receptores do Fator Natriurético Atrial/biossíntese , Testosterona/sangue , Tíbia/anatomia & histologiaRESUMO
Since their discovery in 1981, the cardiac natriuretic peptides (cNP) atrial natriuretic peptide (also referred to as atrial natriuretic factor) and brain natriuretic peptide have been well characterised in terms of their renal and cardiovascular actions. In addition, it has been shown that cNP plasma levels are strong predictors of cardiovascular events and mortality in populations with no apparent heart disease as well as in patients with established cardiac pathology. cNP secretion from the heart is increased by humoral and mechanical stimuli. The clinical significance of cNP plasma levels has been shown to differ in obese and non-obese subjects. Recent lines of evidence suggest important metabolic effects of the cNP system, which has been shown to activate lipolysis, enhance lipid oxidation and mitochondrial respiration. Clinically, these properties lead to browning of white adipose tissue and to increased muscular oxidative capacity. In human association studies in patients without heart disease higher cNP concentrations were observed in lean, insulin-sensitive subjects. Highly elevated cNP levels are generally observed in patients with systolic heart failure or high blood pressure, while obese and type-2 diabetics display reduced cNP levels. Together, these observations suggest that the cNP system plays a role in the pathophysiology of metabolic vascular disease. Understanding this role should help define novel principles in the treatment of cardiometabolic disease.
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Various nutritional supplements (herbs, vitamins, and micronutrients) improve responses and adaptations to resistance exercise. ANP is a heart hormone that contributes to fluid, electrolyte and blood pressure homeostasis through its natriuretic and vasodilative actions. In the present study, the adaptation of ANP in response to resistance exercise was investigated in rats supplemented with glutamine for five weeks. The results showed that supplementation with glutamine did not influence the number of ANP granules per atrial cardiocyte in sedentary animals. In exercised-trained rats, the number and diameter of the granules was significantly higher in comparison with the control group and in exercised animals supplemented with glutamine there was significant increase in the number and diameter of ANP granules compared with controls. Altogether, these data indicated that in resistance exercise rats, glutamine significantly enhances cardiac ANP thus implicating the beneficial effects of glutamine supplementation to the ANP system.
Vários suplementos nutricionais (ervas, vitaminas e micronutrientes) melhoram as respostas e adaptações ao exercício resistido. O ANP é um hormônio cardíaco que contribui para a homeostase de líquidos, eletrólitos e controle da pressão arterial através de suas ações natriurética e vasodilatadora. No presente estudo, a adaptação do ANP em resposta ao treinamento resistido foi investigada em ratos suplementados com glutamina durante cinco semanas. Os resultados mostraram que a suplementação com glutamina não influenciou o número de grânulos de ANP por cardiomiócito em animais sedentários. Em ratos treinados, o número e o diâmetro dos grânulos foi significativamente maior em comparação com o grupo controle e nos animais treinados e suplementados com glutamina houve um aumento significativo no número e diâmetro dos grânulos de ANP comparativamente com os controles. Em conjunto, estes dados indicam que, nos ratos submetidos ao treinamento resistido, a glutamina aumentou significativamente os níveis de ANP cardíaco, mostrando assim, os efeitos benéficos da suplementação com glutamina para o sistema de ANP.
Varios suplementos nutricionales (hierbas, vitaminas y micronutrientes) mejoran las respuestas y adaptaciones al ejercicio de resistencia. El ANP es una hormona cardíaca que contribuye a la homeostasis de fluidos, electrolitos y de control de la presión arterial a través de sus acciones vasodilatadora y natriurética. En el presente estudio, se investigó la adaptación de la ANP en respuesta al entrenamiento de resistencia en ratones suplementados con glutamina durante cinco semanas. Los resultados mostraron que la suplementación de glutamina no influyó en el número de gránulos de ANP por cardiomiocito en animales sedentarios. En ratas entrenadas, el número y el diámetro de los gránulos fue significativamente mayor en comparación con el grupo control y en los animales entrenados y suplementados con glutamina hubo un aumento significativo en el número y diámetro de los gránulos de ANP en comparación con los controles. En conjunto, estos datos indican que en ratones sometidos a entrenamiento de resistencia, la glutamina aumentó significativamente el nivel de ANP cardiaco mostrando de esta manera los efectos beneficiosos de la administración de glutamina para el sistema de ANP.
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Among the topics studied in physiology and aging, a hormone has been drawing attention from the scientificcommunity: the Atrial Natriuretic Peptide (ANP). The ANP, which is produced by the cardiac atria, hasdemonstrated decisive action in endocrine mechanisms of action inhibiting sodium reabsorption in nephrons,revealing a direct influence on physiological mechanisms linked to aging and chronic stress.The overall objectiveof this study was to assess and analyze scientific literature on the ANP in the Pubmed database from 2010 to2012. 30 articles were collected, verifying authorship and gender division of species, instruments and typesof research. The results showed that the research of multiple authorship appeared mostly with 99.1%, being51.8% of male authorship, 17.9% of female authorship and 29.5% of publications not identified. Researchwith only one author appears with 0.8% in total. As the types of species used, it was observed 50.3% of theworks with humans, 40% with animals and 6.7% mixed (animal / human). As to the instruments used, thebiochemical markers were the ones that stood out, with 30%, followed by label arterial pressure with 12, 2%,drugs, with 11.1% and microscopic studies with 10%. In the typology of research, biochemical research appearsfirst, with 33.3%, followed by research morphophysiological/biochemical research, with 30%, Physiological/ biochemical, with 26.7%, Physiological with 6.7% and Morphophysiological with 3.3%. We can concludethat the publications about the hormone ANP are still little explored when the focus is aging. In the analyzedpublications, there is important information about the physiological and biochemical role of ANP as well ason their molecular composition.
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Humanos , Masculino , Feminino , Doenças Cardiovasculares/fisiopatologia , Envelhecimento/fisiologia , Fator Natriurético Atrial/fisiologia , NefropatiasRESUMO
Durante el desarrollo de la hipertensión arterial, las interacciones entre las sobrecargas de presión y de volumen conducen a diferentes patrones de hipertrofia cardíaca y a un aumento de los péptidos natriuréticos (PN). Los perfiles de síntesis y secreción de ANP y BNP se han investigado en modelos de hipertensión arterial; sin embargo, aún no se ha estudiado la evolución diferencial de estos perfiles durante períodos agudos y crónicos de la hipertrofia cardíaca producida por sobrecarga de volumen. Por este motivo estudiamos ratas Sprague- Dawley con el modelo DOCA-sal a las 2, 4, 6 y 12 semanas, correlacionando la evolución de dichos perfiles con la hipertrofia cardíaca y la hipertensión arterial. El grado de hipertrofia cardíaca se correlacionó positivamente con la expresión del ANP en el ventrículo izquierdo y con los niveles de ANP en plasma. La expresión del ANP aumentó a las 4 semanas de tratamiento, mientras que la de BNP se incrementó recién a las 6 semanas. Asimismo, el BNP plasmático se incrementó sólo en el grupo con 12 semanas de tratamiento, mientras que el ANP plasmático mostró un aumento a partir de las 2 semanas de tratamiento. Durante el desarrollo de la hipertrofia cardíaca producida en el modelo DOCA-sal, la síntesis y la secreción de los PN responden en forma diferencial, con incremento precoz del ANP. Además, el aumento de éste superó al de BNP en todos los grupos DOCA-sal, lo que permitiría considerar al ANP como un marcador más específico de la sobrecarga de volumen.
The interactions between pressure and volume overload that occur in hypertension lead to different patterns of cardiac hypertrophy and to increase in natriuretic peptides (NPs). The profiles of ANP and BNP synthesis and secretion have been investigated in models of hypertension; however, the different evolution of these profiles during the acute and chronic periods of pressure overload-induced cardiac hypertrophy is still unknown. For this reason, we studied DOCA-salt treated Sprague-Dawley rats at weeks 2, 4, 6 and 12 and correlated the evolution of these profiles with cardiac hypertrophy and hypertension. Cardiac hypertrophy had a positive correlation with ANP expression in the left ventricle and with ANP plasma levels. BNP expression increased after 4 weeks of treatment while ANP increased significantly after 6 weeks. In addition, BNP plasma levels increased only in the group treated for 12 weeks, while ANP plasma levels increased from week 2. NP secretion has a differential response in the early stages of the development of cardiac hypertrophy induced by the DOCA-salt model, with an early increase in ANP. As ANP levels were exceeded to those of BNP in all the DOCA-salt groups, ANP might be considered a more specific marker of volume overload.