Consequences of perinatal treatment with l-arginine and antioxidants for the renal transcriptome in spontaneously hypertensive rats

Treating spontaneously hypertensive rats (SHR) with l-arginine, taurine, and vitamins C and E (ATCE) during nephrogenesis (2 weeks before to 4 weeks after birth) persistently lowers blood pressure. Hypothetically, differential gene expression in kidney of SHR vs. normotensive Wistar–Kyoto rats (WKY) is partially corrected by maternal ATCE in SHR. Differential gene expression in 2-days, 2-weeks, and 48-week-old rats was studied using oligonucleotide chips. Transcription factor binding sites (TFBS) of differentially expressed genes were analyzed in silico. Differential gene expression varied between SHR+ATCE and SHR, suggesting both direct and indirect effects; but, few genes were modulated toward WKY level and there was little overlap between ages. TFBS analysis suggests less Elk-1-driven gene transcription in both WKY and SHR+ATCE vs. SHR at 2 days and 2 weeks. Concluding, in SHR, persistent antihypertensive effects of maternal ATCE are not primarily due to persistent corrective transcription. Less Elk-1-driven transcription at 2 days and 2 weeks may be involved

Supplementation of bitter melon to rats fed a high-fructose diet during gestation and lactation ameliorates fructose-induced dyslipidemia and hepatic oxidative stress in male offspring

This study examined the impact of maternal high-fructose intake and if metabolic control in the offspring could benefit from supplementing bioactive food components such as bitter melon (BM) to the maternal diet. In Expt. 1, virgin female rats received control (C), high-fructose (F; 60%), or BM-supplemented fructose (FBM; 1%) diet before conception until d 21 of lactation.Weaned male offspring were fed the C diet for 11 wk, forming C/C, F/C, and FBM/C groups. The F/C group had elevated serum insulin, TG, and FFA concentrations and hepatic lipid alterations compared with the C/C and FBM/C groups (P, 0.05). The 2 latter groups did not differ. Expt. 2 had similar dam treatment groups, but offspring were weaned to the C or F diet, forming C/C, C/F, F/F, and FBM/F groups, and the dietary treatment was extended to 20 wk. The hepatic levels of stearyl-CoA desaturase and microsomal TG transfer protein mRNA were lower, but that of PPARg coactivator 1-a and fibroblast growth factor 21 mRNA and fatty acid binding protein 1 protein were higher in the FBM/F group compared with the C/F and F/F groups (P, 0.05), indicating that maternal BM supplementation may reduce lipogenesis and promote lipid oxidation in offspring. The FBM/F group had significantly higher activities of liver glutathione peroxidase, superoxide dismutase, and catalase than the F/F group. The results indicate that supplementing BM to dams could offset the adverse effects of maternal high-fructose intake on lipid metabolism and antioxidant status in adult offspring. © 2011 American Society for Nutrition.link_to_OA_fulltex

Maintenance of Hypertensive Hemodynamics Does Not Depend on ROS in Established Experimental Chronic Kidney Disease

While the presence of oxidative stress in chronic kidney disease (CKD) is well established, its relation to hypertensive renal hemodynamics remains unclear. We hypothesized that once CKD is established blood pressure and renal vascular resistance (RVR) no longer depend on reactive oxygen species. CKD was induced by bilateral ablation of 2/3 of each kidney. Compared to age-matched, sham-operated controls all ablated rats showed proteinuria, decreased glomerular filtration rate (GFR), more renal damage, higher mean arterial pressure (MAP), RVR and excretion of oxidative stress markers and hydrogen peroxide, while excretion of stable nitric oxide (NO) metabolites tended to decrease. We compared MAP, RVR, GFR and fractional excretion of sodium under baseline and during acute Tempol, PEG-catalase or vehicle infusion in rats with established CKD vs. controls. Tempol caused marked reduction in MAP in controls (96±5 vs.79±4 mmHg, P<0.05) but not in CKD (130±5 vs. 127±6 mmHg). PEG-catalase reduced MAP in both groups (controls: 102±2 vs. 94±4 mmHg, P<0.05; CKD: 118±4 vs. 110±4 mmHg, P<0.05), but did not normalize MAP in CKD rats. Tempol and PEG-catalase slightly decreased RVR in both groups. Fractional excretion of sodium was increased by both Tempol and PEG-catalase in both groups. PEG-catalase decreased TBARS excretion in both groups. In sum, although oxidative stress markers were increased, MAP and RVR did not depend more on oxidative stress in CKD than in controls. Therefore reactive oxygen species appear not to be important direct determinants of hypertensive renal hemodynamics in this model of established CKD

Designing and implementing sample and data collection for an international genetics study: The Type 1 Diabetes Genetics Consortium (T1DGC)

Background and Purpose The Type 1 Diabetes Genetics Consortium (T1DGC) is an international project whose primary aims are to: (a) discover genes that modify type 1 diabetes risk; and (b) expand upon the existing genetic resources for type 1 diabetes research. The initial goal was to collect 2500 affected sibling pair (ASP) families worldwide. Methods T1DGC was organized into four regional networks (Asia-Pacific, Europe, North America, and the United Kingdom) and a Coordinating Center. A Steering Committee, with representatives from each network, the Coordinating Center, and the funding organizations, was responsible for T1DGC operations. The Coordinating Center, with regional network representatives, developed study documents and data systems. Each network established laboratories for: DNA extraction and cell line production; human leukocyte antigen genotyping; and autoantibody measurement. Samples were tracked from the point of collection, processed at network laboratories and stored for deposit at National Institute for Diabetes and Digestive and Kidney Diseases (NIDDK) Central Repositories. Phenotypic data were collected and entered into the study database maintained by the Coordinating Center. Results T1DGC achieved its original ASP recruitment goal. In response to research design changes, the T1DGC infrastructure also recruited trios, cases, and controls. Results of genetic analyses have identified many novel regions that affect susceptibility to type 1 diabetes. T1DGC created a resource of data and samples that is accessible to the research community. Limitations Participation in T1DGC was declined by some countries due to study requirements for the processing of samples at network laboratories and/or final deposition of samples in NIDDK Central Repositories. Re-contact of participants was not included in informed consent templates, preventing collection of additional samples for functional studies. Conclusions T1DGC implemented a distributed, regional network structure to reach ASP recruitment targets. The infrastructure proved robust and flexible enough to accommodate additional recruitment. T1DGC has established significant resources that provide a basis for future discovery in the study of type 1 diabetes genetics. © The Author(s) 2010

ATP, P2 receptors and the renal microcirculation

Purinoceptors are rapidly becoming recognised as important regulators of tissue and organ function. Renal expression of P2 receptors is broad and diverse, as reflected by the fact that P2 receptors have been identified in virtually every major tubular/vascular element. While P2 receptor expression by these renal structures is recognised, the physiological functions that they serve remains to be clarified. Renal vascular P2 receptor expression is complex and poorly understood. Evidence suggests that different complements of P2 receptors are expressed by individual renal vascular segments. This unique distribution has given rise to the postulate that P2 receptors are important for renal vascular function, including regulation of preglomerular resistance and autoregulatory behaviour. More recent studies have also uncovered evidence that hypertension reduces renal vascular reactivity to P2 receptor stimulation in concert with compromised autoregulatory capability. This review will consolidate findings related to the role of P2 receptors in regulating renal microvascular function and will present areas of controversy related to the respective roles of ATP and adenosine in autoregulatory resistance adjustments