e 517Objective: Distal tubular sodium retention is a potent driver of hypertension, with the thiazide sensitive sodium chloride cotransporter (NCC) and its phosphorylated form (pNCC) key players. The upstream modulators of NCC expression and phosphorylation are unclear, but some evidence suggests that mineralocorticoid receptor (MR) activation by aldosterone may be involved. The synthetic mineralocorticoid fludrocortisone is a potent MR agonist. In this project we aimed to quantify the magnitude and time course of changes in expression pNCC in human urinary exosomes, in response to activation of the MR by oral fludrocortisone administration.Design and method: Daily "spot" morning urine samples were collected from 20 patients undergoing fludrocortisone suppression testing (100mcg q6 h) to diagnose or exclude primary aldosteronism. Urinary exosomes were isolated by progressive ultracentrifugation and NCC and pNCC expression quantified by western blot, expressed as arbitrary units of optical density (OD) / mg creatinine. Results:A progressive rise in NCC and pNCC expression was observed, with median NCC increasing >3 fold, from 3.37 OD/ug to 11.38 OD/ug. Median pNCC increased >2 fold, from 5.29 OD/ug to 14.30 OD/ug. In a mixed effects model a change of +2.12 OD/ug per day (p < 0.0005) was estimated for NCC expression, and +2.32 OD/ug per day (p < 0.0005) for pNCC.Conclusions: MR activation causes a rapid (<24 hours) and progressive increase in NCC and pNCC expression in humans. This widens the potential role of aldosterone in regulating distal sodium handling and has implications regarding treatment options for hypertension with MR blockade.Objective: Single nucleotide polymorphisms (SNPs) can contribute to development and progression of cardiovascular disease (CVD). Left ventricular diastolic dysfunction (LVDD) is a well-recognized complication of hypertension and a predictor of CVD. However, the association between SNPs and LV function remains unclear. Therefore, we investigated the association between left ventricular diastolic function parameters and SNPs in Polish hypertensive cohort. Design and method:We studied 744 hypertensive patients (mean age 54.7 ± 13.6 years) from the Care North cohort. LV function was defined as left atrium size (LA), E/A, E' and E/E'. All subjects were genotyped for 25 SNPs previously shown to be associated with myocardial infarction and coronary artery disease. SNP with minor allele frequency (MAF)<5% and with missing values>10% were excluded (n = 3). Missing values of each SNP were imputed with random forest method. Linear regression assuming an additive model was applied to identify and compare the effect size of tested SNPs. Models were adjusted for age, 24-hr systolic and diastolic blood pressure, and heart rate. Results:The analysis showed 8 of 25 studied SNPs to be significantly associated with E, E/E' and LA. E -Early diastolic mitral flow velocity, E' -early diastolic mitral annulus velocity, LA -Left atrium area Conclusions: Our study reveals that SNPs previously linked to c...

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Object: to identify factors that limit the effectiveness of pharmacotherapy of hypertension (HT) with comorbid coronary artery disease (CAD) in elderly obese patients by determining laboratory and spectroscopy features related to inflammation. Material and methods: 60 patients (68.2 ± 5.9 y.o.) were observed and treated in Internal Medicine Department of University Clinic of Odessa National Medical University. Patients were divided into 2 groups. The 1st group included patients (n = 30) with body mass index (BMI) ≤25 kg/m2, HT and co-morbid CAD; the 2nd group (n = 30) - patients with BMI≥30 kg/m2, HT and with co-morbid CAD. For each patient’s group antihypertensive combination of Lisinopril and Bisoprolol was prescribed. The Laser correlation spectroscopy (LCS) was a special method for investigation. Results: before pharmacotherapy (PT) in both groups according to LCS 11-150 nm particles are prevailing. But in obese patients 75th percentile of 31-70 nm particles exceeds that one in non-obese group (56.7% vs 30.5%). During PT systolic blood pressure (SBP) value normalized in the patients of 1st group (without obesity), while in the obese patients (2nd group) SBP remained above target level. Creatinine level increased in patients of  1st group (without obesity) by 16.5 μmol / L (p <0.05) with a decrease in GFR by 17.1 ml/min/1.73 m2 (P <0.05). LCS data during PT show increase of 11-30 nm and decrease of 75-150 nm particles in non-obese patients, while in obese patients 71-150 nm particles are prevailing and 150 nm particles have appeared (p<0.05). Conclusions: 1. In elderly hypertensive patients with concomitant CAD, obesity is a factor limiting the effectiveness of complex antihypertensive therapy. 2. An increase of proportion of allergic-directed and appearance of autoimmune-directed homeostatic shifts in serum according to LCS are associated with a decrease of antihypertensive therapy efficacy in elderly hypertensive patients with CAD and obesity.  3. In hypertensive non-obese patients with CAD under the influence of complex antihypertensive therapy deteriorating of renal function is observed while in obesity renal function is not changed. 4. Homeostatic changes revealed in the second group by LCS values probably reflect manifestation of  low grade inflammatory process caused by excessive activity of adipose tissue.