Aim      To study the functional condition of sympathoadrenal system as evaluated by beta-adrenoreactivity of erythrocyte membranes (beta-ARM) during two years following renal denervation (RD) in patients with resistant arterial hypertension (RAH) and to determine the relationship of this index with long-term antihypertensive and cardioprotective effectivity of this invasive treatment. Material and methods The study included 48 patients (mean age, 57.2±8.7 years, 18 men) with RAH on a stable antihypertensive therapy. Averaged daily systolic and diastolic blood pressure (SBP and DBP) and levels of beta-ARM were determined at baseline and in 7 days and 2 years following RD. Measurement of beta-ARM was based on beta-adrenoblocker inhibition of erythrocyte hemolysis induced by exposure to hypo-osmotic environment. The beta-adrenoblocker binds to erythrocyte membrane beta-adrenoceptors to prevent the erythrocyte destruction. Increased values of beta-ARM reflect a decrease in the number of functionally active erythrocyte membrane beta-adrenoceptors associated with long-term sympathetic hyperactivity. Results For two years of follow-up, values of average daily BP decreased from 160.4±16.0 / 88.1±14.6 to 145.3±19.3 / 79.4±13.6 mm Hg. At 7 days, the number of beta-ARM had decreased in the group of RD responders (р=0.028) who at two years had decreased their BP by 10 mm Hg or more, while in the group of non-responders, the number of beta-ARM remained unchanged. At one week, beta-ARM values correlated with changes in SBP and DBP (r= –0.54; р<0.05) and with left ventricular myocardial mass (LVMM) (r= –0.36; р<0.05) at two years of follow-up whereas beta-ARM delta at one week was interrelated with the renin concentration in the long-term (r= –0.44; р<0.05). At two years, the content of beta-ARM was increased in both groups. Conclusion The decrease in beta-ARM content at 7 days after RD shows the procedure efficacy and allows an expectation of clinically significant decreases in BP and LVMM in the long-term after the surgical treatment. At two years after the intervention, the content of beta-ARM increased, and the BP decrease was apparently due to some other mechanisms.

Aim. To assess the association of CYP2C19 G681A, P2RY12 H1/H2, and ITGB3 T1565C polymorphisms with the extent of platelet aggregation in patients with coronary heart disease (CHD) during antiplatelet therapy. Subjects and methods. 166 male patients with CHD, living in the Western Siberian Region, were examined. All the patients underwent a test for platelet aggregation induced by ADP (2.5 and 5.0 µm) and epinephrine (0.2 µm). Genotyping was performed using an allele-specific polymerase chain reaction technique. Results. The polymorphic variants of the P2RY12 and ITGB3 genes were ascertained to have no impact on the extent of platelet aggregation in patients receiving clopidogrel and acetylsalicylic acid. An association was found between CYP2C19 681A allele carriage and the increased extent of platelet aggregation induced by ADP. Conclusion. The carriage of the cytochrome P450 CYP2C19 681A allele rather than platelet receptor gene polymorphisms determines a risk for clopidogrel resistance in patients with CHD.

Introduction. Patients with resistant hypertension (RHTN) and type 2 diabetes mellitus (T2DM) are characterized by sympathetic hyperactivity. A promising method for the assessment is a measurement of erythrocyte membrane beta-adrenergic reactivity (β-ARM). However, little is known about β-ARM in patients with RHTN and T2DM.Purpose. To investigate the properties of β-ARM of erythrocytes in patients with RHTN and T2DM in relation to clinical, laboratory, and instrumental data.Material and Methods. The cross-sectional study comprised 38 patients with RHTN combined with T2DM with mean age of 62.1 ± 7 years (25 women (65.8%)), 24-hour systolic/diastolic blood pressure (24-BP) (SBP/DBP) of 160.3 ± 14.2/90.8 ± 10.5 mm Hg, and glycated hemoglobin (HbA1c) of 7.2 ± 1.4%. The comparison group comprised 24 patients with RHTN without T2DM, which did not significantly differ in sex and age. General clinical examinations, measurements 24-BP and office blood pressure, β-ARM, HbA1c, 24-hour urine, echocardiography, and 24-hour electrocardiography with the assessment of heart rate variability (HRV) with low-frequency (LF) and high-frequency (HF) components were performed in all patients.Research Results. In both groups, β-ARM was significantly higher than the normal value corresponding to 20 conventional units (CU): 45.9 ± 21.9 and 41.3 ± 18.9 for patients with RHTN+T2DM and RHTN without T2DM, respectively, p = 0.39. The incidence of increase in β-ARM was comparable: 82% in RHTN with T2DM patients and 88% in RHTN without T2DM patients, χ2 = 0.38, p = 0.537. The β-ARM values correlated with duration of hypertension (R = 0.31), SBP-24 variability (R = 0.36), LF (R = 0.60), and HF (R = –0.53)) values according to HRV, 24-hour urine volume (R = –0.32), left ventricular parameters (ejection fraction (R = 0.42), ventricular efficiency (R = –0.36), arterioventricular coupling (R = –0.40)), duration of T2DM (R = –0.45), and HbA1c level (R = –0.55).Conclusions. RHTN patients were characterized by a high frequency of β-ARM increase, whether or not T2DM was present, although a long and severe course of T2DM was associated with lower values of this indicator. According to the data from instrumental studies, β-ARM in patients with RHTN and T2DM was quantitatively related to the markers of sympathetic activity, which correlated with the duration of hypertension and parameters of renal and left ventricular functional status.

Aim. To investigate time course of changes in the adrenoreactivity (AR) of erythrocyte membranes (EM) after radiofrequency ablation of the synaptic nerves of the renal arteries (RA) in patients with resistant hypertension (RH) and to assess whether this indicator can be used for the early evaluation of the efficiency of an invasive intervention into the RA. Subjects and methods. 24 patients with RH, who received full-dose antihypertensive therapy with at least three drugs, including a diuretic, were examined. Renal sympathetic denervation (RSD) was carried out by endovascular radiofrequency ablation (RFA) of the RA. 24-hour blood pressure (BP) monitoring and determination of the β-adrenoreactivity (β-AR) of EM were performed, by taking into account the change in erythrocyte osmoresistence at baseline and 1 and 24 weeks after RFA. The therapy was not changed during the observation. Results. The patients included in the study were divided into 2 groups. One week following RSD, 15 patients of Group 1 were noted to have a decrease in the β-AR of EM by 10 conditional units or more; average daily systolic BP (SBP) and diastolic BP (DBP) reduced by 8.3 and 2.8 mm Hg, respectively. In 9 patients of Group 2, the β-AR of EM was unchanged in this observation period or increased compared with baseline. In this group, the decrease in average daily SBP and DBP was noted to be less pronounced than that in Group 1 (by 1.4 and 1.5 mm Hg, respectively). At 24 weeks after RSD, Group 1 was seen to have an effective daily decrease in average daily SBP and DBP by 25.6 and 14.3 mm Hg, respectively (p=0.01 and 0.05). The average value of the β-AR of EM significantly declined compared with baseline. In Group 2, no statistically significant changes were reported; SPB and DBP lowered by 7.0 and 3.0 mm Hg, respectively. There was a significant decrease in the β-AR of EM compared with that at week 1. Conclusion. The decline in the β-AR of EM within the first week after RFA is suggestive of the decreased activity of the sympathoadrenal system and may be used as an early efficiency index of RSD after the procedure.