Objective.To evaluate the plasma levels of metalloproteinases (MMP) and their inhibitor in patients with resistant hypertension (RHTN) and type 2 diabetes mellitus (DM2) and their relationship with renal blood flow and kidney function.Design and methods.The study included 18 patients with RHTN and DM2 and 16 individuals with RHTN without DM, who underwent offce and 24-h ambulatory blood pressure measurements, renal Doppler ultrasound, and laboratory tests (daily albuminuria, estimated glomerular fltration rate calculated by CKD-EPI formula, HbА1c and basal glycaemia levels, MMP-9, MMP-2, tissue inhibitor of MMP type 1 (TIMP1), MMP/TIMP-1 ratios).Results.Patients with RHTN and DM2 and subjects with RHTN without DM were comparable by mean levels of metalloproteinases, TIMP-1, and their ratios. The frequency of increased MMP-9 level was similar in both groups (61 % for RHTN + DM2 group and 75 % for RHTN without DM, p > 0,05). In patients with RHTN and DM2 the increase in MMP-9 and a decrease in TIMP-1/MMP-9 ratio were associated with a reduction in renal resistive indices (MMP-9 and RI in the main renal arteries: right-sided R = –0,60, p = 0,009, left-sided R = –0,60, p = 0,008; in segmental arteries: R = –0,49, p = 0,038 on the right and R = –0,59, p = 0,012 on the left; for TIMP-1/MMP-9 and segmental arteries: R = 0,51, p = 0,028 on the right; and R = 0,46, p = 0,04 on the left). The eGFR and MMP-9 signifcantly correlated (R = 0,55, p = 0,023). Patients with increased albuminuria showed higher values of TIMP-1/MMP-2 ratio than patients with normal albuminuria (2,97 ± 0,82 и 1,58 ± 0,33 ng/mL, respectively, p = 0,03). There was a direct correlation between TIMP-1/MMP-2 ratio and basal glycaemia (R = 0,59, p = 0,018).Conclusions.Patients with RHTN and DM2 had comparable MMP levels and their inhibitor to those in patients with RHTN without DM, which may partly reflect that extracellular matrix formation is independent from carbohydrate disorders in RHTN. In patients with RHTN and DM2 an increase in MMP-9 and a decrease in TIMP-1/MMP-9 ratio may be adaptive, since it is accompanied by improved intrarenal blood flow and renal fltration function. The increase in basal hyperglycemia is associated with the suppression of the proteolytic activity of MMP-2 related to the progression of albuminuria.
Aim. To compare cardioprotective effects of two renal denervation (RD) techniques: main renal artery or its branches after bifurcation in patients with resistant hypertension (RH).Materials and methods. This randomized double-blind clinical (ClinicalTrials. gov. identifier: NCT02667912) study with a follow-up of 12,3±1,6 months included 55 patients with RH, which was divided into 2 groups: group 1 (n=27) — main renal artery denervation; group 2 — RD of branches. Mean age of patients was 57,3±9,5 and 56,4±9,3 years, respectively. We assessed structural and functional cardiac characteristics using two-dimensional speckle-tracking echocardiography (STE).Results. Initially, the patients in the groups did not differ in terms of studied parameters and therapy. After RD in both groups, the levels of myocardial stress significantly decreased; 95% confidence interval: after main renal artery denervation — systolic [-4802; -2896], diastolic [-3264; -2032] dyne/cm2; after RD of branches — [-6324; -5328] and [-4021; -2521] dyne/cm2, respectively (p=0,001 and 0,024, respectively). After main renal artery denervation, there was a decrease in the left ventricular (LV) wall thickness (interventricular septum [1,06; -0,62] and posterior wall [0,12; -0,62]) in comparison with RD of branches ([-0,68; -1,28] and [-0,68; -1,06], respectively). These differences were significant: p=0,023 and 0,021, respectively. After distal RD, decrease in the LV mass was observed more often by 21,2%, an increase in the LV mass was 2 times less frequent. Restoration of diastolic function was more common in patients after distal RD than main renal artery denervation (26% vs 13%, respectively). According to pilot analysis, STE parameters was also improved.Conclusion. Twelve months after distal RD, compared with the main renal artery denervation, the LV wall thickness, number of patients with LV hypertro -phy, and diastolic dysfunction decreased significantly greater. Two-dimensional STE revealed improvement of cardiac parameters. The results require further research.
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