Hormones

May 2012

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.

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Hormones

Ilona Kurnatowska 2 3 10 Piotr Grzelak 1 3 9 Magdalena Kaczmarska 1 3 9 Anna Masajtis-Zagajewska 2 3 10 Ludomir Stefanczyk 1 3 9 Michal Nowicki 2 3 10 0 Inserm Unit 872-E2 , Paris France 1 Department of Radiology and Diagnostic Imaging, Medical University of dz , Poland 2 Department of Nephrology , Hypertension and Kidney Transplantation, Medical University of dz , Poland 3 Liliana Simes-Silva 4 Dpt de Nphrologie, Universit de Montral , Hpital Du Sacr-Coeur, Montral, Canada 5 Inserm U1018, Centre de Recherche En Epidmiologie Et Sant Publique , Villejuif, France 6 Inserm U872-E2, Paris, France 7 -diderot; Ap-Hp, Hpital Bichat, Diabtologie, Paris, France 8 National Research Institute of Mother and Child , Warsaw, Poland 9 Department of Nephrology and Internal Diseases, Medical University of Warsaw , Warsaw, Poland 10 Department of Nephrology, Military Institute of Medicine , Warsaw, Poland 11 Warsaw Medical University 12 Department of Internal Diseases and Endocrynology, Medical University of Warsaw , Warsaw, Poland RENAL AND INTESTINAL GUANYLIN PEPTIDES SYSTEM IN A MOUSE MODEL OF DIET-INDUCED OBESITY - 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 Fundao para a Cincia e Tecnologia/FEDER. INFLUENCE OF SMOKING ON PLASMA VASOPRESSIN AND URINE CONCENTRATION IN A FRENCH MIDDLE-AGED POPULATION (THE D.E.S.I.R. COHORT) 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 analyses. Non parametric tests (Spearmans 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. SEX HORMONE LEVELS AND CORONARY CALCIFICATION IN POSTMENOPAUSAL WOMEN WITH CHRONIC KIDNEY DISEASE STAGE 3-5 Introduction and Aims: It has recently been found that both estrogens and testosterone may inhibit vascular calcification but the role of sex hormones in the development of cardiovascular complications in chronic kidney disease (CKD) is still unclear. The aim of the study was to assess the relations between sex hormones, coronary artery calcification (CAC) and atherosclerosis in postmenopausal women with CKD stage 3-5. Methods: In a cross-sectional s (...truncated)


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Liliana Simões-Silva, Mónica Moreira-Rodrigues, Janete Quelhas-Santos, Cátia Fernandes-Cerqueira, Manuel Pestana, Isabel Soares-Silva, Benedita Sampaio-Maia, Lise Bankir, Fezeu Leopold, Bouby Nadine, Ronan Roussel, Beverley Balkau, Marre Michel, Bichet Daniel, Ilona Kurnatowska, Piotr Grzelak, Magdalena Kaczmarska, Anna Masajtis-Zagajewska, Ludomir Stefanczyk, Michal Nowicki, Stanislaw Niemczyk, Longin Niemczyk, Katarzyna Szamotulska, Zbigniew Bartoszewicz, Ivanna Dubchak, Urszula Syta, Joanna Matuszkiewicz-Rowińska, Stanislaw Niemczyk, Marta Dudek, Zbigniew Bartoszewicz, Katarzyna Szamotulska, Dorota Brodowska, Łukasz Woźniacki, Longin Niemczyk, Malǵorzata Gomólka, Urszula Syta, Aleksandra Rymarz, Antonio Lacquaniti, Valentina Donato, Maria Rosaria Fazio, Silvia Lucisano, Valeria Cernaro, Rosaria Lupica, Michele Buemi. Hormones, 2012, pp. ii330-ii332, 27/suppl 2, DOI: 10.1093/ndt/gfs233