Hormones

Nephrology Dialysis Transplantation 27 (Supplement 2): ii330–ii332, 2012 doi:10.1093/ndt/gfs233 HORMONES SAP046 RENAL AND INTESTINAL GUANYLIN PEPTIDES SYSTEM IN A MOUSE MODEL OF DIET-INDUCED OBESITY Liliana Simões-Silva1, Mónica Moreira-Rodrigues2, Janete Quelhas-Santos3, Cátia Fernandes-Cerqueira1, Manuel Pestana3, Isabel Soares-Silva1 and Benedita Sampaio-Maia1 1 Unit of Research and Development of Nephrology, Faculty of Medicine, University of Porto, Porto, Portugal, 2Institute of Pharmacology and Therapeutics, Faculty of Medicine, University of Porto, Porto, Portugal, 3Unit of Research and Development of Nephrology, Faculty of Medicine, University of Porto, Portugal Introduction and Aims: Obesity has reached epidemic proportions world-wide and is associated with several complications like coronary heart disease and hypertension. The association between obesity and hypertension is well documented. Yet, how obesity raises blood pressure remains less clear. Guanylin peptides regulate electrolytes and water transport in intestinal and renal epithelia. The aim of the present study was to evaluate the activity of the Guanylin peptides system (GPS) and its role on the regulation of sodium balance in a mouse model of diet- induced obesity. Methods: Male C57BL/6J mice were submitted to either a high-fat high-simple carbohydrate diet (obese mice) or a normal diet (control mice). The renal and intestinal ( jejunum and colon) guanylin, uroguanylin and GC-C receptor mRNA expression were evaluated by qPCR in control and obese mice, during normo (NS) and high-saline (HS) diet, induced by oral consumption of 1% NaCl for 3 days. Results: Obese mice presented glucose intolerance and insulin resistance that were accompanied by a significant increase in both systolic and diastolic blood pressures. During the first day of HS diet, the urinary sodium excretion was reduced by ~30% in obese mice in comparison to controls. During NS diet, obese mice presented reduced mRNA expression of GN and UGN in colon ( p = 0.019; p = 0.032) as well as GC-C in jejunum ( p = 0.037) and colon ( p = 0.041) whereas the UGN mRNA expression was increased in renal cortex ( p = 0.005). During HS diet, obese mice presented reduced mRNA expression of UGN in jejunum ( p = 0.0002) as well as GN and GC-C in jejunum ( p = 0.041; p = 0.0004) and colon ( p = 0.008; p = 0.0001). Conclusions: The data obtained suggest that in a mouse model of diet-induced obesity a down-regulation of intestinal GPS is accompanied by a compensatory increase of renal GPS activity. These results suggest that GPS may play a role in compromised sodium handling in obesity. BSM is supported by the fellowship SFRH/BPD/21782/2005 from Fundação para a Ciência e Tecnologia/FEDER. SAP047 analyses. Non parametric tests (Spearman’s rank correlation coefficients and Wilcoxon rank- sum test, with correction of ties when appropriate) were used to test the associations. PVP results are shown as medians and [25-75% percentiles], and UD values (no unit) as means ± SD. Corresponding approximate urine osmolarity (Uosm) is shown. Results: PVP ranged from 0.5 to 17.8 pg/ml, and UD from 1000 to 1030. PVP was not associated with age, body mass index or physical exercise. PVP was highest in current smokers (Current-S), intermediate in ex-smokers (Ex-S) and lowest in non-smokers (Non-S) (see table). The difference between Current-S and Non-S was significant ( p = 0.019), but not that between Ex- S and Current-S. SAP047 Table 1 In Current-S, PVP was positively associated with the number of cigarettes/day ( p = 0.013). As could be expected, PVP was positively and strongly correlated with UD (rho = 0.21, p = 0.0001). UD in Current-S was significantly higher than in Non-S ( p = 0.002) and marginally higher than in Ex-S ( p = 0.055). PVP and UD were both higher in males than in females (significant only for PVP) (see table). SAP047 Table 2 Conclusions: To our knowledge, this is the first study evaluating the influence of smoking status on vasopressin in a general population. The present results suggest that smoking almost doubles baseline PVP and increases urine concentration by approximately 100 mosm/l. Men exhibit 75 % higher vasopressin and a borderline higher urine concentration than women. Because vasopressin was shown to increase GFR and albuminuria and to accelerate progression of chronic kidney disease (CKD) in several animal models, the present results suggest that the faster progression of CKD seen in men vs women and the adverse effect of smoking may be, at least in part, mediated by a higher VP secretion and the resulting higher urine concentration. INFLUENCE OF SMOKING ON PLASMA VASOPRESSIN AND URINE CONCENTRATION IN A FRENCH MIDDLE-AGED POPULATION (THE D.E.S.I.R. COHORT) Lise Bankir1, Fezeu Leopold2, Bouby Nadine3, Ronan Roussel4, Beverley Balkau5, Marre Michel6 and Bichet Daniel7 1 Inserm Unit 872-E2, 2Inserm U872-E2, Centre de Recherche des Cordeliers, Paris, France, 3Inserm Unit 872-E2, Paris France, 4Inserm U872-E2, Paris, France, 5Inserm U1018, Centre de Recherche En Epidémiologie Et Santé Publique, Villejuif, France, 6Université Paris*–diderot; Ap-Hp, Hôpital Bichat, Diabétologie, Paris, France, 7Dépt de Néphrologie, Université de Montréal, Hôpital Du Sacré-Coeur, Montréal, Canada Introduction and Aims: Several studies have shown that acute tobacco smoking or nicotine administration increases vasopressin (VP) secretion. To our knowledge, no study has investigated whether plasma VP concentration (PVP) or urine concentration differ according to the chronic smoking status in the general population. Methods: The study population was 498 French men and women, aged 30-65 years, from the D.E.S.I.R. study participants (Data from an Epidemiological Study on Insulin Resistance Syndrome). During the baseline visit, they received health examinations including blood drawing for various analyses, and collection of a spot urine sample. They answered a self-administered questionnaire with reports of mean daily intake of various nutrients and beverages, physical exercise, and smoking status (current smokers, ex-smokers or non-smokers) including the number of cigarettes/ day for current smokers. PVP at baseline was measured by radioimmunoassay, and urine density (UD), an index of urine concentration, was determined with Multistix® reagent strips. Values of PVP lower than the detection threshold of the assay (0.5 pg/ml) were considered equal to the threshold. PVP was log-transformed for statistical SAP048 SEX HORMONE LEVELS AND CORONARY CALCIFICATION IN POSTMENOPAUSAL WOMEN WITH CHRONIC KIDNEY DISEASE STAGE 3-5 Ilona Kurnatowska1, Piotr Grzelak2, Magdalena Kaczmarska2, Anna Masajtis-Zagajewska1, Ludomir Stefanczyk2 and Michal Nowicki1 1 Department of Nephrology, Hypertension and Kidney Transplantation, Medical University of Łódz, Poland, 2Department of Radiology and Diagnostic Imaging, Medical University of Łódz , Poland Introduction and Aims: It has re (...truncated)