Browsing by Author "Sousa, Frederico Barros de"

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    An orally active angiotensin-(1–7) inclusion compound and exercisetraining produce similar cardiovascular effects in spontaneouslyhypertensive rats.
    (2014) Bertagnolli, Mariane; Casali, Karina Rabello; Sousa, Frederico Barros de; Rigatto, Katya; Oliveira, Lenice Kappes Becker; Santos, Sergio Henrique Sousa; Dias, Lucinara Dadda; Pinto, Graziela; Dartora, Daniela Ravizzoni; Schaan, Beatriz D'Agord; Milan, Ruben Dario Sinisterra; Irigoyen, Maria Claudia; Santos, Robson Augusto Souza dos
    Low angiotensin-(1–7) (Ang-(1–7)) concentration is observed in some cardiovascular diseases and exer-cise training seems to restore its concentration in the heart. Recently, a novel formulation of an orallyactive Ang-(1–7) included in hydroxy-propyl-beta-cyclodextrin (HPB-CD) was developed and chronicallyadministered in experimental models of cardiovascular diseases. The present study examined whetherchronic administration of HPB-CD/Ang-(1–7) produces beneficial cardiovascular effects in spontaneouslyhypertensive rats (SHR), as well as to compare the results obtained with those produced by exercisetraining. Male SHR (15-week old) were divided in control (tap water) or treated with HPB-CD/Ang-(1–7)(corresponding to 30 _g kg−1day−1of Ang-(1–7)) by gavage, concomitantly or not to exercise training(treadmill, 10 weeks). After chronic treatment, hemodynamic, morphometric and molecular analysis inthe heart were performed. Chronic HPB-CD/Ang-(1–7) decreased arterial blood pressure (BP) and heartrate in SHR. The inclusion compound significantly improved left ventricular (LV) end-diastolic pressure,restored the maximum and minimum derivatives (dP/dT) and decreased cardiac hypertrophy index inSHR. Chronic treatment improved autonomic control by attenuating sympathetic modulation on heartand vessels and the SAP variability, as well as increasing parasympathetic modulation and HR variability.Overall results were similar to those obtained with exercise training. These results show that chronictreatment with the HPB-CD/Ang-(1–7) inclusion compound produced beneficial effects in SHR resem-bling the ones produced by exercise training. This observation reinforces the potential cardiovasculartherapeutic effect of this novel peptide formulation.
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    Discovery and characterization of Alamandine : a novel component of the Renin-Angiotensin system.
    (2013) Lautner, Roberto Queiroga; Villela, Daniel Campos; Silva, Rodrigo Araújo Fraga da; Silva, Neiva Caldeira; Braga, Thiago Verano; Fraga, Fabiana Costa; Jankowski, Joachim; Jankowski, Vera; Sousa, Frederico Barros de; Alzamora, Andréia Carvalho; Soares, Everton Rocha; Barbosa, Claudiane Maria; Kjeldsen, Frank; Oliveira, Aline Cristina; Braga, Janaina Félix; Savergnini, Silvia Silveira Quintão; Etelvino, Gisele Maia; Peluso, Antonio Augusto Bastos; Silva, Danielle Gomes Passos; Ferreira, Anderson José; Alves, Fabiana; Martins, Almir de Sousa; Raizada, Mohan K.; Paula, Renata Dutra de; Santos, Daisy Motta; Klempin, Friederike; Pimenta, Adriano Monteiro de Castro; Alenina, Natalia; Sinisterra Millán, Ruben Dario; Bader, Michael; Santos, Maria José Campagnole dos; Santos, Robson Augusto Souza dos
    The renin–angiotensin system (RAS) is a key regulator of the cardiovascular system, electrolyte, and water balance. Here, we report identification and characterization of alamandine, a new heptapeptide generated by catalytic action of angiotensin-converting enzyme-2 angiotensin A or directly from angiotensin-(1–7). To characterize a novel component of the RAS, alamandine. Using mass spectrometry we observed that alamandine circulates in human blood and can be formed from angiotensin-(1–7) in the heart. Alamandine produces several physiological actions that resemble those produced by angiotensin-(1–7), including vasodilation, antifibrosis, antihypertensive, and central effects. Interestingly, our data reveal that its actions are independent of the known vasodilator receptors of the RAS, Mas, and angiotensin II type 2 receptor. Rather, we demonstrate that alamandine acts through the Mas-related G-protein–coupled receptor, member D. Binding of alamandine to Mas-related G-protein–coupled receptor, member D is blocked by D-Pro7-angiotensin-(1–7), the Mas-related G-protein–coupled receptor, member D ligand β-alanine and PD123319, but not by the Mas antagonist A-779. In addition, oral administration of an inclusion compound of alamandine/β-hydroxypropyl cyclodextrin produced a long-term antihypertensive effect in spontaneously hypertensive rats and antifibrotic effects in isoproterenol-treated rats. Alamandine had no noticeable proliferative or antiproliferative effect in human tumoral cell lines. The identification of these 2 novel components of the RAS, alamandine and its receptor, provides new insights for the understanding of the physiological and pathophysiological role of the RAS and may help to develop new therapeutic strategies for treating human cardiovascular diseases and other related disorders.
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    Investigation of spatially localized defects in synthetic WS2 monolayers.
    (2022) Rosa, Bárbara Luiza Teixeira; Fujisawa, Kazunori; Cruz, Joyce Cristina da; Zhang, Tianyi; Matos, Matheus Josué de Souza; Sousa, Frederico Barros de; Barbosa, Tiago Campolina; Fonseca, Lucas Lafetá Prates da; Ramos, Sérgio L. L. M.; Carvalho, Bruno Ricardo de; Chacham, Helio; Neves, Bernardo Ruegger Almeida; Terrones, Mauricio; Moreira, Leandro Malard
    While the spatially nonhomogeneous light emission from synthetic WS2 monolayers is frequently reported in the literature, the nature of this phenomenon still requires thoughtful investigation. Here, we combine several characterization techniques (optical imaging, scanning probe and electron microscopy) along with density func- tional theory to investigate the presence of substitutional doping localized at narrow regions along the S zigzag edge of WS2 monolayers. We verified that photoluminescence quenching along narrow regions is not related to grain boundaries but to substitutional impurities of lighter metals at the W sites, which modify the radiative and nonradiative decay channels. We also found potential candidates for occupying the W site through ADF-STEM analysis and discussed their impact on photoluminescence quenching by performing density functional theory calculations. Our findings shed light on how atomic defects introduced during WS2 monolayer’s synthesis impact the crystalline quality and, therefore, the development of high-performance optoelectronic devices based on semiconducting 2D materials.
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    Structural and physical–chemical evaluation of bradykinin potentiating peptide and its high soluble supramolecular complex.
    (2010) Sousa, Frederico Barros de; Denadai, Ângelo Márcio Leite; Lula, Ivana Silva; Ianzer, Danielle Alves; Malaspina, Érica Resende; Camargo, Antônio Carlos Martins de; Santos, Robson Augusto Souza dos; Sinisterra, Ruben Dario
    The supramolecular interactions between a Bradykinin Potentiating Peptide (BPP10c) and b-cyclodextrin (bCD) have been investigated by using several techniques. These new properties acquired by the inclusion phenomena are important in developing a strategy for pharmaceutical formulation. The BPP10c structural elucidation and its inclusion complex formed have been investigated using Nuclear Magnetic Resonance techniques. The peptide secondary structure was investigated using infrared spectroscopy in solution, Circular Dichroism and NMR. In addition, the thermodynamic parameters of the inclusion process were also evaluated using Isothermal Titration Calorimetry. The results obtained by these physical– chemical techniques suggested a 1:1 complex formed by interaction between the Tryptophan amino acid residue and the bCD cavity. The peptide secondary structure was not substantially modified for the inclusion process. In addition, the inclusion process proved to be spontaneous (DG8 = -2.53 kcal mol-1), with an enthalpy reduction (DH8 = -3.72 kcal mol-1) and a favored entropic variation (TDS8 = -1.19 kcal mol-1).