Browsing by Author "Barbosa, Claudiane Maria"

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    Different reactive species modulate the hypotensive effect triggered by angiotensins at CVLM of 2K1C hypertensive rats.
    (2020) Sousa, Graziele Galdino de; Barbosa, Maria Andréa; Barbosa, Claudiane Maria; Lima, Taynara Carolina; Santos, Robson Augusto Souza dos; Santos, Maria José Campagnole dos; Alzamora, Andréia Carvalho
    Hypertension is associated with increased central activity of the renin-angiotensin system (RAS) and oxidative stress. Here, we evaluated whether reactive species and neurotransmitters could contribute to the hypotensive effect induced by angiotensin (Ang) II and Ang-(1− 7) at the caudal ventrolateral medulla (CVLM) in renovascular hypertensive rats (2K1C). Therefore, we investigated the effect of Ang II, Ang-(1-7), and the Ang-(1-7) antagonist A-779 microinjected before and after CVLM microinjection of the nitric oxide (NO)-synthase inhibitor, (L-NAME), vitamin C (Vit C), bicuculline, or kynurenic acid in 2K1C and SHAM rats. Baseline values of the mean arterial pressure (MAP) in 2K1C rats were higher than in SHAM rats. CVLM microinjection of Ang II, Ang-(1− 7), L-NAME, or bicuculline induced decreases in the MAP in SHAM and 2K1C rats. In addition, Vit C and A-779 produced decreases in the MAP only in 2K1C rats. Kynurenic acid increased the MAP in both SHAM and 2K1C rats. Only the Ang-(1− 7) effect was increased by L-NAME and reduced by bicuculline in SHAM rats. L-NAME also reduced the A-779 effect in 2K1C rats. Only the Ang II effect was abolished by CVLM Vit C and enhanced by CVLM kynurenic acid in SHAM and 2K1C rats. Overall, the superoxide anion and glutamate participated in the hypotensive effect of Ang II, while NO and GABA participated in the hypotensive effect of Ang-(1− 7) in CVLM. The higher hypotensive response of A-779 in the CVLM of 2K1C rats suggests that Ang-(1− 7) contributes to renovascular hypertension.
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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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    Efeitos da exposição de ratos à dieta hiperlipídica sobre parâmetros cardiometabólicos das proles F1 e F2.
    (2018) Barbosa, Claudiane Maria; Alzamora, Andréia Carvalho; Cardoso, Leonardo Máximo; Alzamora, Andréia Carvalho; Costa, Daniela Caldeira; Leite, Romulo
    A má alimentação dos progenitores pode predispor a prole a doenças cardiometabólicas. O objetivo desse estudo foi investigar se a dieta hiperlipídica (H) submetida aos progenitores predispõe a prole a distúrbios cardiometabólicos. Para isso ratos Fischer foram submetidos à dieta H (G0HM e G0HF) ou controle (C) (G0CM e G0CF) durante o acasalamento, gestação e lactação, gerando as proles F1 (F1HM e F1CM) ou (F1HF e F1CF). Parte das proles F1 (F1HM e F1CM) ou (F1HF e F1CF) foram acasalados e tornaram-se os genitores G1 (G1HM e G1HF) ou (G1CM e G1CF), e suas proles divididas em (F2HM e F2CM) ou (F2HF e F2CF). Todas as proles F1 e F2 consumiram dieta C após desmame até completar 90 dias de idade. Avaliou-se os parâmetros nutricionais, biométricos, bioquímicos e hemodinâmicos. Os progenitores G0HM apresentaram aumento da PAM (PAM), FC (bpm) e massa corporal (g). As progenitoras apresentaram resistência à insulina (ng/ml), aumento do índice de adiposidade, dos níveis de triglicérides (mg/dL), da ingesta energética (Kcal), aumento relativo do pâncreas (g/100g), da glicemia (mg/dL), do HOMA-IR e da PAM. Os ratos F1HM (n=6-14) e F1HF (n= 6-9) apresentaram aumento da PAM (123±4 e 122±3; respectivamente), maior queda da PAM induzida pelo hexametônio (ms/mmHg) (-56±2 e -44±5; respectivamente), da ingesta de água (ml) (238±12 e 164±8; respectivamente), ingesta calórica (791±12 e 587±11; respectivamente) e alimentar (g) (226±5 e 168±6; respectivamente), o depósito de gordura retroperitoneal (g/100g) (5,9±4 e 5,0±0,3; respectivamente), o índice de adiposidade (18±1,4 e 7±0,4; respectivamente), a massa corporal (341±1 e 218±5; respectivamente), a glicemia de jejum (138±2 e 129±4; respectivamente), e triglicérides (176±10 e 180±10; respectivamente) comparado aos grupos F1CM (n=6-16) e F1CF (n=6-18). Os ratos F2HM (n=7-12) e F2HF (8-15) apresentaram aumento a PAM (127±1 e 130±5; respectivamente), maior queda da PAM induzida pelo hexametônio (-46±1 e -42±2; respectivamente), a ingesta de água (257±10 e 188±8; respectivamente), ingesta alimentar (233±7 e 176±6; respectivamente) e calórica (812±13 e 608±12; respectivamente), peso relativo do fígado (g/100g) (3,4±0,1 e 3,5±0,1; respectivamente), o índice de adiposidade (13±0,2 e 7,7±0,1; respectivamente), massa corporal (336±3 e 209±2; respectivamente), a glicemia de jejum (124±2 e 123±7; respectivamente), o colesterol total (mg/dL) (93±2 e 103±3; respectivamente) e os triglicérides (142±8 e 169±9; respectivamente) comparado aos grupos F2CM (n= 8-11) e F2CF (n=8-12). Nossos dados mostram que a dieta H materna durante o acasalamento, gestação e lactação induziu distúrbios característicos da SM nas proles F1 e F2 mesmo estas sendo alimentadas com dieta C após desmame. Além disso, esses distúrbios cardiometabólicos foram de maior extensão nas proles F2 em relação as proles F1.
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    Hypotensive effect induced by microinjection of Alamandine, a derivative of angiotensin-(1–7), into caudal ventrolateral medulla of 2K1C hypertensive rats.
    (2017) Soares, Everton Rocha; Barbosa, Claudiane Maria; Santos, Maria José Campagnole dos; Santos, Robson Augusto Souza dos; Alzamora, Andréia Carvalho
    In the present study we evaluated the cardiovascular effects produced by microinjection of the new component of the renin-angiotensin system, alamandine, into caudal ventrolateral medulla of urethane-anesthetized normotensive and hypertensive 2K1C rats. The participation of different angiotensin receptors in the effects of alamandine was also evaluated. Microinjection of angiotensin-(1–7) was used for comparison. The microinjection of 4, 40 and 140 pmol of alamandine or angiotensin-(1–7) into caudal ventrolateral medulla induced similar hypotensive effects in Sham-operated rats. However, contrasting with angiotensin-(1–7), in 2K1C rats the MAP response to the highest dose of alamandine was similar to that observed with saline. The microinjection of A- 779, a selective Mas receptor antagonist, blunted the angiotensin-(1–7) effects but did not block the hypotensive effect of alamandine in Sham or in 2K1C rats. However, microinjection of D-Pro7-angiotensin-(1–7), a Mas/MrgD receptor antagonist, blocked the hypotensive effect induced by both peptides. Furthermore, microinjection of PD123319, a putative AT2 receptor antagonist blocked the hypotensive effect of alamandine, but not of angiotensin-( 1–7), in Sham and 2K1C rats. Microinjection of the AT1 receptor antagonist, losartan, did not alter the hypotensive effect of angiotensin-(1–7) or alamandine in both groups. These results provide new insights about the differential mechanisms participating in the central cardiovascular effects of alamandine and angiotensin- (1–7) in normotensive and 2K1C hypertensive rats.
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    Ingestão de dieta hiperlipídica por ratas progenitoras induz aumento da ingesta calórica, inflamação sistêmica e disbiose na prole da segunda geração.
    (2022) Barbosa, Claudiane Maria; Alzamora, Andréia Carvalho; Alzamora, Andréia Carvalho; Costa, Daniela Caldeira; Moreira, Leandro Marcio; Vieira, Maria Aparecida Ribeiro; Campos, Wellington Garcia de
    Este trabalho apresenta os efeitos da dieta hiperlipídica (DH) consumida pela progenitora (G0) nos distúrbios cardiometabólicos e na microbiota intestinal na prole segunda geração (F2). Ratos submetidos a DH (G0H) ou dieta controle (DC) (G0C) durante o período de acasalamento, gestação e lactação, geraram a prole F2 (F2-G0H e F2-G0C, respectivamente), que receberam apenas DC. Ambos, G0H e F2G0H, apresentaram alterações na microbiota intestinal, aumento da PAM, níveis plasmáticos de TAG, índice de adiposidade e processo inflamatório no depósito de gordura retroperitoneal e no cólon evidenciado pelo aumento da expressão gênica de TNF-α, MCP-1, MyD-88 e CAV-1. Além disso, a prole F2-G0H apresentou aumento da ingestão alimentar, resistência à leptina, colesterol total e níveis plasmáticos de MCP-1 e redução de adiponectina. Em relação às comunidades microbianas, observou-se maior diversidade com 5 famílias de bactérias exclusivas que foram correlacionadas com distúrbios cardiometabólicos. Em geral, a progenitora induziu aumento na ingestão alimentar, inflamação sistêmica e alterações na microbiota na prole F2G0H.
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    Maternal high-fat diet triggers metabolic syndrome disorders that are transferred to first and second offspring generations.
    (2020) Barbosa, Claudiane Maria; Figueiredo, Vivian Paulino; Barbosa, Maria Andréa; Cardoso, Leonardo Máximo; Alzamora, Andréia Carvalho
    A high-fat (H) diet increases metabolic disorders in offspring. However, there is great variability in the literature regarding the time of exposure, composition of the H diets offered to the genitors and/or offspring and parameters evaluated. Here, we investigated the effect of a H diet subjected to the genitors on different cardio-metabolic parameters on first (F1)- and second (F2)-generation offspring. Female Fischer rats, during mating, gestation and breast-feeding, were subjected to the H diet (G0HF) or control (G0CF) diets. Part of F1 offspring becomes G1 genitors for generating the F2 offspring. After weaning, F1 and F2 rats consumed only the C diet. Nutritional, biometric, biochemical and haemodynamic parameters were evaluated. G0HF genitors had a reduction in food intake but energy intake was similar to the control group. Compared with the control group, the F1H and F2H offspring presented increased plasma leptin, insulin and fasting glucose levels, dietary intake, energy intake, adiposity index, mean arterial pressure, sympathetic drive evidenced by the hexamethonium and insulin resistance. Our data showed that only during mating, gestation and breast-feeding, maternal H diet induced cardio-metabolic disorders characteristic of human metabolic syndrome that were transferred to both females and males of F1 and F2 offspring, even if they were fed control diet after weaning. This process probably occurs due to the disturbance in mechanisms related to leptin that increases energy intake in F1H and F2H offspring. The present data reinforce the importance of balanced diet during pregnancy and breast-feeding for the health of the F1 and F2 offspring.
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    The novel Angiotensin-(1-7) analog, A-1317, improves insulin resistance by restoring pancreatic β-Cell functionality in rats with metabolic syndrome.
    (2020) Barbosa, Maria Andréa; Barbosa, Claudiane Maria; Lima, Taynara Carolina; Santos, Robson Augusto Souza dos; Alzamora, Andréia Carvalho
    In previous studies we have shown that oral Ang-(1–7) has a beneficial therapeutic effect on cardiometabolic disturbances present in metabolic syndrome (MetS). Based on the fact that Ang-(1–7) acts through release of nitric oxide (NO), a new peptide, A-1317 was engineered adding the amino acid L-Arginine, the NO precursor, to the N-terminal portion of the Ang-(1– 7). Therefore, in a single molecule the substrate and the activator of NO are combined. In the present study, we evaluated the effect of A-1317 oral treatment on liver-glucose metabolism in MetS induced by high fat (HF) diet in rats. Rats were subjected to control (AIN-93M, CT) or HF diets for 15 weeks to induce MetS and treated with A-1317, Ang-(1–7) included into hydroxypropyl-b-cyclodextrin (HPbCD) or empty HPbCD (E), in the last 7 weeks. At the end of 15 weeks, hemodynamic, biometric, and biochemical parameters, redox process, and qRT-PCR gene expression of NO synthase and RAS components were evaluated in the liver. HF/E rats increased body mass gain, adiposity index, despite the reduction in food intake, increased plasma leptin, total cholesterol, triglycerides, ALT, fasting blood glucose, OGTT and insulin, HOMA-IR and MAP and HR. Furthermore, the MetS rats presented increased in liver angiotensinogen, AT1R, ACE mRNA gene expression and concentration of MDA and carbonylated protein. Both Ang-(1–7) and A-1317 oral treatment in MetS rats reverted most of these alterations. However, A-1317 was more efficient in reducing body mass gain, ALT, AST, total cholesterol, insulin, fasting blood glucose, ameliorating b cell capacity by increasing HOMA-b and QUICKI, whereas Ang-(1–7) reduced HOMA-b and QUICKI. In addition, Ang- (1–7) increased Mas and AKT liver mRNA gene expression, while A-1317 increased both Mas and MRGD and AMPK liver mRNA gene expression, suggesting a distinct pathway of action of Ang-(1–7) and A-1317 in MetS rats. Taken together, our data showed that treatment with A-1317 was able to ameliorate MetS disorders and suggested that this effect was mainly via MRGD via activation of AMPK and increasing b cell function.