Increased intrarenal renin-angiotensin system activity contributes to diabetic nephropathy. ANG II generation in mesangial cells (MC) is increased by high-glucose (HG) exposure. This study assessed the mechanisms involved in the glucose-induced ANG II generation in rat MC. Under basal conditions, MC mainly secreted prorenin. HG decreased prorenin secretion and induced a striking 30-fold increase in intracellular renin activity. After 72 h of HG exposure, only the mRNA levels for angiotensinogen and angiotensin-converting enzyme (ACE) were significantly elevated. However, after shorter periods of 24 h of HG stimulation the mRNA levels of the enzymes prorenin and cathepsin B, besides that for ACE, were significantly increased. The results suggest that the HG-induced increase in ANG II generation in MC results from an increase in intracellular renin activity mediated by at least three factors: a time-dependent stimulation of (pro)renin gene transcription, a reduction in prorenin enzyme secretion, and an increased rate of conversion of prorenin to active renin, probably mediated by cathepsin B. The increase in angiotensinogen mRNA in parallel to increased renin activity indicates that HG also increased the availability of the renin substrate. The consistent upregulation of ACE mRNA suggests that, besides renin, ACE is directly involved in the increased mesangial ANG II generation induced by HG.

It was analyzed the forms of renin produced by a mouse immortalized mesangial cell line (MIC) and their ability to generate angiotensin II (AII). The synthesis, localization and secretion of renin and AII by MIC were evaluated under conditions of normal (10 mM) or high (30 mM) glucose concentration. Two major bands of 35 kDa and 70 kDa were observed in SDS-PAGE. The amino-terminal sequencing reveled the presence of prorenin and renin in these bands with higher homology with the submaxillary gland form of renin. Renin and AII were detected in cell lysate and in culture medium, indicating that MIC synthesize and secrete these peptides. Renin was localized in the cytoplasm while AII was seen predominantly inside the nucleus. High glucose induced an increase in the synthesis and secretion of renin and AII. Results suggest that MIC produce AII and a renin form similar to the submandibular. Intracellular AII may be directed at the nucleus and/or be secreted, indicating that AII may directly influences gene expression in these cells. The mechanisms of synthesis and secretion of renin and AII are potentially modified by high glucose concentration, suggesting a possible role of AII produced by mesangial cells in diabetic nephropathy.

Objective: To analyze the results of isolated on-pump coronary artery bypass graft surgery (CABG) in patients ≥ 65 years-old.Methods: Patients undergoing isolated on-pump CABG from December 1 st 2010 to July 31 th 2012 were divided in two groups: GE (elderly ≥ 65 years-old, n=103) and GA (adults < 65 years-old, n=150). Preoperative data, intraoperative (as cardiopulmonar bypass time, aortic clamping time, time length of stay in mechanical ventilation -MV -and number of grafts), and postoperative variable (as morbidity, mortality and time length of stay in hospital) were analyzed during hospitalization.Results: In GE, the morbidity rate was greater than in GA (30% vs. 14%, P=0.004), but there was no difference in the mortality rate (5.8% vs. 2.0%, P=0.165). In GA, there was higher prevalence DM (39.6% vs. 27%, P=0.043) and smoking (32.2% versus 19.8%, P=0.042); and in GE, higher prevalence of stroke (17% vs. 6.7%, P=0.013). There was no difference between the groups regarding intraoperative variables. After multivariate analysis, age ≥ 65-year-old was associated with greater morbidity, but it was not independent predictive factor for in-hospital mortality. Considering in-hospital mortality, stay in ward time length (P=0.006), cardiac (P=0.011) and respiratory complications (P=0.026) were independent predictive factors.Conclusion: This study suggests that patients ≥ 65-yearold were at increased risk of postoperative complications when submitted to isolated on-pump CABG in comparison to patients < 65-year-old, but not under increased risk of death.

No abstract

Children with obesity have a high risk of developing cardiovascular disease and hypertension, which is associated with the renin-angiotensin system (RAS) activation and kallikrein-kinin system (KKS) inactivation. Although recent studies have identified several peptide-based biomarkers for obesity, circulating peptides from the RAS and KKS in adolescents with obesity have not been described. The aim of this study was to examine circulating levels of RAS and KKS peptides in adolescents with obesity to investigate the turnover of these peptides and their relationship to metabolic disorders resulting from weight gain. The subjects (n = 104) were divided into normal weight (NW), overweight (OW), obese (OB), and morbidly obese (MO) groups. Anthropometric profiles were created by measuring height, weight, blood pressure, and skinfolds. Plasma levels of Ang I, II, (1-7), BK, and des-Arg 9 BK were quantified by high-performance liquid chromatography. The levels were as follows:

No abstract

No abstract

Accumulation of HSP70 is related to the cytoprotection. It was evaluated whether hyperosmotic stress induces HSP70 accumulation in LLC-PK1 cells, and protects cells against toxicity provoked by cisplatin (Cis) and cyclosporine A (CyA). Cells were maintained in isosmotic (Iso) or hyperosmotic (H) culture medium for 24 h and then exposed to Cis or CyA for an additional period of 12 or 24 h (groups H+Cis and H+CyA). The H medium did not induce cell death and increased both HSP70 mRNA and protein levels, suggesting a role in cell adaptation to H condition. H medium produced partial cytoprotection against Cis and CyA compared with control cells. Despite the cytoprotection, there was a reduction in HSP70 mRNA and protein levels in H+Cis group. In contrast, the H+CyA group presented high levels of HSP70 mRNA and protein. The induction of HSP70 by H medium was associated with tolerance of LLC-PK1 cells against Cis and CyA cytotoxicity but this protection was induced by different mechanisms and depended on the characteristics of the drug used.