JOEL CLAUDIO HEIMANN
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Clínica Médica, Faculdade de Medicina - Docente
LIM/16 - Laboratório de Fisiopatologia Renal, Hospital das Clínicas, Faculdade de Medicina - Líder
LIM/16 - Laboratório de Fisiopatologia Renal, Hospital das Clínicas, Faculdade de Medicina - Líder
4 resultados
Resultados de Busca
Agora exibindo 1 - 4 de 4
- Maternal high-sodium intake alters the responsiveness of the renin-angiotensin system in adult offspring(2012) RAMOS, Debora R.; COSTA, Nauilo L.; JANG, Karen L. L.; OLIVEIRA, Ivone B.; SILVA, Alexandre A. da; HEIMANN, Joel C.; FURUKAWA, Luzia N. S.Aims: The goal of the current study was to evaluate the impact of maternal sodium intake during gestation on the systemic and renal renin-angiotensin-aldosterone-system (RAAS) of the adult offspring. Main methods: Female Wistar rats were fed high- (HSD-8.0% NaCl) or normal-sodium diets (NSD-1.3% NaCl) from 8 weeks of age until the delivery of their first litter. After birth, the offspring received NSD. Tail-cuff blood pressure (TcBP) was measured in the offspring between 6 and 12 weeks of age. At 12 weeks of age, the offspring were subjected to either one week of HSD or low sodium diet (LSD-0.1 6%NaCl) feeding to evaluate RAAS responsiveness or to acute saline overload to examine sodium excretory function. Plasma (PRA) and renal renin content (RRC), serum aldosterone (ALDO) levels, and renal cortical and medullary renin mRNA expression levels were evaluated at the end of the study. Key findings: TcBP was higher among dams fed HSD, but no TcBP differences were observed among the offspring. Male offspring, however, exhibited increased TcBP after one week of HSD feeding, and this effect was independent of maternal diet. Increased RAAS responsiveness to the HSD and LSD was also observed in male offspring. The baseline levels of PRA. ALDO, and cortical and medullary renin gene expression were lower but the RRC levels were higher among HSD-fed male offspring (HSDoff). Conversely, female HSDoff showed reduced sodium excretion 4 h after saline overload compared with female NSDoff. Significance: High maternal sodium intake is associated with gender-specific changes in RAAS responsiveness among adult offspring.
- A novel peptide that improves metabolic parameters without adverse central nervous system effects(2017) RECKZIEGEL, Patricia; FESTUCCIA, William T.; BRITTO, Luiz R. G.; JANG, Karen L. Lopes; ROMAO, Carolina M.; HEIMANN, Joel C.; FOGACA, Manoela V.; RODRIGUES, Naielly S.; SILVA, Nicole R.; GUIMARAES, Francisco S.; EICHLER, Rosangela A. S.; GUPTA, Achla; GOMES, Ivone; DEVI, Lakshmi A.; HEIMANN, Andrea S.; FERRO, Emer S.Intracellular peptides generated by limited proteolysis are likely to function inside and outside cells and could represent new possibilities for drug development. Here, we used several conformational-sensitive antibodies targeting G-protein coupled receptors to screen for novel pharmacological active peptides. We find that one of these peptides, DITADDEPLT activates cannabinoid type 1 receptors. Single amino acid modifications identified a novel peptide, DIIADDEPLT (Pep19), with slightly better inverse agonist activity at cannabinoid type 1 receptors. Pep19 induced uncoupling protein 1 expression in both white adipose tissue and 3T3-L1 differentiated adipocytes; in the latter, Pep19 activates pERK1/2 and AKT signaling pathways. Uncoupling protein 1 expression induced by Pep19 in 3T3-L1 differentiated adipocytes is blocked by AM251, a cannabinoid type 1 receptors antagonist. Oral administration of Pep19 into diet-induced obese Wistar rats significantly reduces adiposity index, whole body weight, glucose, triacylglycerol, cholesterol and blood pressure, without altering heart rate; changes in the number and size of adipocytes were also observed. Pep19 has no central nervous system effects as suggested by the lack of brain c-Fos expression, cell toxicity, induction of the cannabinoid tetrad, depressive-and anxiety-like behaviors. Therefore, Pep19 has several advantages over previously identified peripherally active cannabinoid compounds, and could have clinical applications.
- Longitudinal changes in blood pressure are preceded by changes in albuminuria and accelerated by increasing dietary sodium intake(2023) KATAYAMA, Isis Akemi; HUANG, Yuefei; GARZA, Amanda E.; BROOKS, Danielle L.; WILLIAMS, Jonathan S.; NASCIMENTO, Mariana M.; HEIMANN, Joel C.; POJOGA, Luminita H.Background: Dietary sodium is a well-known risk factor for cardiovascular and renal disease; however, direct evidence of the longitudinal changes that occur with aging, and the influence of dietary sodium on the age-associated alterations are scarce. Methods: C57BL/6 mice were maintained for 13 months on a low (LS, 0.02 % Na+), normal (NS, 0.3 % Na+) or high (HS, 1.6 % Na+) salt diet. We assessed 1) the longitudinal trajectories for two markers of cardiovascular and renal dysfunction (blood pressure (BP) and albuminuria), as well as hormonal changes, and 2) end-of-study cardiac and renal parameters. Results: The effect of aging on BP and kidney damage did not reach significance levels in the LS group; however, relative to baseline, there were significant increases in these parameters for animals maintained on NS and HS diets, starting as early as month 7 and month 5, respectively. Furthermore, changes in albuminuria preceded the changes in BP relative to baseline, irrespective of the diet. Circulating aldosterone and plasma renin activity displayed the expected decreasing trends with age and dietary sodium loading. As compared to LS - higher dietary sodium consumption associated with increasing trends in left ventricular mass and volume indices, consistent with an eccentric dilated phenotype. Functional and molecular markers of kidney dysfunction dis-played similar trends with increasing long-term sodium levels: higher renovascular resistance, increased glomerular volumes, as well as higher levels of renal angiotensin II type 1 and mineralocorticoid receptors, and lower renal Klotho levels. Conclusion: Our study provides a timeline for the development of cardiorenal dysfunction with aging, and doc-uments that increasing dietary salt accelerates the age-induced phenotypes. In addition, we propose albuminuria as a prognostic biomarker for the future development of hypertension. Last, we identified functional and mo-lecular markers of renal dysfunction that associate with long-term dietary salt loading.
conferenceObject Glucose metabolism and DNA methylation of offspring are altered by maternal sodium restriction(2013) SIQUEIRA, Flavia Ramos; PhuongSon Nguyen; KOBZIK, Lester; OLIVEIRA, Ivone Braga de; HEIMANN, Joel Claudio; FURUKAWA, Luzia Naoko ShinoharaObjective: To evaluate glucose metabolism of adult offspring of dams fed low sodium diet during pregnancy. Methods: Female Wistar rats (n= 6 – 8/group) were fed low (LS- 0.15%) or normal (NS-1.3% NaCl) salt diet since the 1st day of gestation until delivery or LS during 1st (LS10) or 2 nd half of gestation (LS20). Body weight (BW), circulating glucose, insulin, leptin and C-peptide levels, glucose (GTT) and insulin tolerance test (ITT) and leptin receptor (LR) methylation were measured in male (M) and female (F) offspring at 12 weeks of age Results (mean±SEM, p< 0.05): BW, at birth (g, n=14 – 27/group) (M: NS = 6.5±0.1, LS = 5.5±0.1, LS10 = 6±0.1, LS20 = 4.8±0.1, F: NS = 6±0.2, LS = 5±0.1, LS10 = 6±0.1, LS20 = 4±0.1) was lower in LS, LS10 and LS20 than in NS, while at adulthood it was not different. Glucose was higher in LS (M=115±3; F=110±4) than in the other groups (M: NS=103±1; LS10=100±2; LS20=96±2; F:NS=101±2; LS10=100±2; 108±2). C-peptide was higher in LS (M=1117±152; F=509±27) than in NS (M=375±41; F=233±63) and lower in LS20 (M=97±15; F=76±9) compared to LS10 (M=528±112; F=378±45).Glucose was higher in LS M and F at 5 minutes of the GTT compared to NS offspring. Leptin, insulin, and ITT were not different. But LR methylation was increased in LS20. Conclusion: Sodium restriction during pregnancy leads to low birth weight and to modifications of glucose metabolism and LR methylation.