Good Antihypertensive Effect Research Articles

Clinical effectiveness of amlodipine/indapamide/perindopril fixed-dose combination in patients with metabolic disorders: results of post hoc analyzes of the TRICOLOR study

Aim. To describe antihypertensive effectiveness of triple fixed-dose combination of am lo dipine/indapamide/perindopril and assess predictors of its clinical effectiveness in pati ents depending on body mass index (BMI) and presence of type 2 diabetes (T2D).Material and methods. This observational prospective study TRICOLOR (NCT03722524) (n=1247) demonstrated high antihypertensive effectiveness and good tolerability of amlodipine/indapamide/perindopril fixed-dose combination. Subgroup analyzes based on BMI included data from 1144 patients. In a second subgroup analysis, 1128 patients were stratified according to concomitant T2D.Results. In patients with overweight/obesity and diabetes, good antihypertensive effectiveness of amlodipine/indapamide/perindopril was observed, comparable in blood pressure (BP) reduction with the comparison groups (patients with normal BMI and patients without diabetes). At the same time, patients with normal BMI, compared with patients with overweight and obesity, had significantly lower systolic BP (SBP) (after 4 and 12 weeks) and diastolic BP (DBP) (after 2 and 12 weeks). In the subgroups, depending on the diabetes status, there were no significant differences in the decrease in SBP and DBP levels at all follow-up points. By the 12th week, BP decrease in the group of patients with normal BMI was 32,9 (10,5)/15,3 (8,6) mm Hg, in the group with overweight — 33,2 (11,3)/14,2 (8,5) mm Hg, in the obesity group — 33,9 (12,3)/14,1 (8,8) mm Hg (p>0,05 for intergroup comparison). Target BP <140/90 mm Hg already after 2 weeks of therapy achieved a higher number of patients with a normal BMI compared to overweight group (50,8% vs 37,2%, p=0,009). By the 12th week, the vast majority of patients, regardless of BMI and diabetes status, achieved a target BP <140/90 mm Hg, which demonstrates a good and rapid response to triple fixed-dose therapy.Conclusion. Thus, additional analyzes of the TRICOLOR study demonstrate the high antihypertensive effectiveness of amlodipine/indapamide/perindopril in hypertensive patients, regardless of the presence of diabetes, overweight or obesity.

Maximakinin reversed H2O2 induced oxidative damage in rat cardiac H9c2 cells through AMPK/Akt and AMPK/ERK1/2 signaling pathways

Maximakinin (MK), a homolog of bradykinin (BK), is extracted from skin venom of the Chinese toad Bombina maxima. Although MK has a good antihypertensive effect, its effect on myocardial cells is unclear. This study investigates the protective effect of MK on hydrogen peroxide (H2O2)-induced oxidative damage in rat cardiac H9c2 cells and explores its mechanism of action. A 3-(4,5-Dimethyl-2-Thiazolyl)-2,5-Diphenyl Tetrazolium Bromide (MTT) assay was selected to detect the effect of MK on H9c2 cell viability, while flow cytometry was used to investigate the influence of MK and H2O2 on intracellular reactive oxygen species (ROS) levels. Protein expression changes were detected by western blot. In addition, specific protein inhibitors were applied to confirm the induction of ROS-related signaling pathways by MK. MTT assay results show that MK significantly reversed H2O2-induced cell growth inhibition. Flow cytometry Dichlorodihydrofluorescein diacetate (DCFH-DA) staining shows that MK significantly reversed H2O2-induced increases in intracellular ROS production in H9c2 cells. Moreover, the addition of specific protein inhibitors suggests that MK reverses H2O2-induced oxidative damage by activating AMP-activated protein kinase (AMPK)/protein kinase B (Akt) and AMPK/extracellular-regulated kinase 1/2 (ERK1/2) pathways. Finally, an inhibitor of bradykinin B2 receptors (B2Rs), HOE-140, was applied to investigate potential targets of MK in H9c2 cells. HOE-140 significantly blocked induction of AMPK/Akt and AMPK/ERK1/2 pathways by MK, suggesting a potentially important role for B2Rs in MK reversing H2O2-induced oxidative damage. Above all, MK protects against oxidative damage by inhibiting H2O2-induced ROS production in H9c2 cells. The protective mechanism of MK may be achieved by activation of B2Rs to activate downstream AMPK/Akt and AMPK/ERK1/2 pathways.

New data from a subanalysis of the TRICOLOR study: antihypertensive effectiveness of the triple single-pill combination of amlodipine/indapamide/perindopril and predictors of effectiveness and blood pressure control in young patients

Aim. To describe the antihypertensive efficacy of triple fixed­dose combination of amlodipine/indapamide/perindopril and assess the predictors of efficacy in young patients (<50 years).Material and methods. The TRICOLOR study (NCT03722524) is an observational prospective study (n=1247) that demonstrated high antihypertensive effectiveness and good tolerability of the triple single­pill combination (SPC) of amlodipine/ indapamide/perindopril. This subgroup analysis was performed on 199 patients aged <50 years (16% of the total population), and the comparison group consisted of 925 patients (82,3% of the total population) aged 50 years or older.Results. In young patients, during triple therapy with SPC amlodipine/indapa­ mide/perindopril, a positive trend in blood pressure (BP) reduction was observed compared to the baseline: an average decrease in BP after 12 weeks was 32,6 (11,0)/14,8 (8,5) mm Hg (p<0,0001), comparable to patients over 50 years of age in terms of reduction in systolic blood pressure (SBP) and diastolic blood pressure (DBP) after 2, 4 and 12 weeks of follow­up. A greater number of young patients achieved a reduction in blood pressure <140/90 mm Hg after 2 weeks of therapy compared to patients 50 years of age and older (49,7% vs 38,8%, p=0,004), and blood pressure <130/80 mm Hg – after 4 and 12 weeks (51,3% vs 43,5% (p=0,041) and 74,9% vs 67,5% (p=0,038), respectively). Left ventricular hypertrophy was a significant negative predictor of SBP reduction by 12 weeks of therapy, and the presence of grade 2 hypertension (HTN) and statin use, on the contrary, were positive predictors of changes in SBP by the end of observation. More adherent younger patients were significantly more likely to have a decrease in DBP by 12 weeks of follow-up. In addition, in young patients, male sex and the presence of dyslipidemia significantly increased the chances of blood pressure control at the end of observation. Waist circumference, body mass index, and grade 2 HTN were negative predictors of achieving the target blood pressure level.Conclusion. Thus, in young patients, good antihypertensive effectiveness of amlodipine/indapamide/perindopril was observed, comparable in the degree of blood pressure reduction with the older age group of 50 years and older.

Study of the Mechanism Underlying the Antihypertensive Effects of Eucommia ulmoides and Tribulus terrestris Based on an Analysis of the Intestinal Microbiota and Metabonomics.

The combination of Eucommia ulmoides and Tribulus terrestris (ET) has been widely utilized in clinical practice for thousands of years, but the mechanism underlying its efficacy has not been elucidated to date. This study attempted to investigate the role played by the intestinal microbiota and fecal metabolism in the response of elderly spontaneous hypertensive rats (SHRs) to ET administration as a treatment for hypertension. Fourteen male spontaneously hypertensive rats (SHRs, 18 months old) were randomly divided into an ET group and an SHR group, and 7 Wistar-Kyoto (WKY) rats of the same age were employed as the control group. The ET group was intragastrically administered 1.0 g/kg/d ET for 42 days, and SHRs and WKY rats were administered an equal amount of normal saline intragastrically. The intestinal microbiota and fecal metabolism were analyzed by 16S rRNA sequencing and the GC-MS (gas chromatography-mass spectrometry)/MS assay. ET treatment decreased blood pressure steadily, improved the colonic tissue morphology, and changed the structure and composition of the imbalanced microbiota in SHRs. Specifically, ET treatment increased the abundance of Eubacterium, which might be one of the target microbes for ET, and had a negative correlation with the levels of α-tocopherol, chenodeoxycholic acid, and deoxycholic acid according to the Spearman correlation analysis. The change in the intestinal microbiota affected the fecal metabolic pattern of SHRs. Eight potential biomarkers were determined to be primarily enriched in ABC transporters, phenylalanine metabolism, central carbon metabolism in cancer, purine metabolism, and protein digestion and absorption. The correlation analysis demonstrated that the abundance of Eubacterium and the decreased levels of α-tocopherol, chenodeoxycholic acid, and deoxycholic acid in the ET group were highly correlated. Our results suggest that ET has a good antihypertensive effect, which may be driven by the intestinal microbiota and their beneficial metabolites. The results of this study may help to elucidate the antihypertensive mechanism of ET.

THE DAILY EXCRETION OF CATECHOLAMINES IN THE URINE OF NORMOTENSIVE PATIENTS WITH DIABETES WITHOUT HYPERTENSION

As you know, judge the state of the tone and reactivity of SAS allows the study of the excretion of the catecholamines (KA), of metabolic products of biogenic amines and enzymes involved in their metabolism. More informative and appropriate for clinical trials is a systematic approach to the study of SAS, including simultaneous determination of excretion of the precursor of the synthesis of KA - DOPA and its spectrum: dopamine (DA), noradrenaline (NA) and adrenaline (A) [8]. In available for us literature data on this problem is quite contradictory and relates to certain aspects of these studies. Installed as the decrease or increase in the level of CA in blood and urine, as in type 2 diabetes [4,5] and in hypertension [7,8,9]. There are no works devoted to the study of the qualitative and quantitative assessment of the functional state of the sympathetic-adrenal system, i.e. excretion of KA and their precursors and activity of monoamine oxidase (MAO) when combined with diabetes 2-type with AG. It is known that one of the processes that lead to the disruption of the cell membrane is the activation of processes of peroxide oxidation of lipids (Pol). Excessive formation of free radicals, accumulation of primary and secondary products of lipoperoxidation weakens the hydrophobic membrane when the body's cells, in particular β-cells of the islets of Langerhans, which leads ultimately to the suppression of proinsulin synthesis and cell death [5]. From the foregoing it is obvious that the state of the sympathetic-adrenal system and processes of lipid peroxidation in type 2 diabetes with hypertension has been insufficiently studied, and the available results are contradictory. Accordingly, this issue remains controversial. An urgent task is the development of optimal approaches to the treatment of hypertension in patients with type 2 diabetes. Ideally, such a drug should have a good antihypertensive effect, but must be at least metabolically neutral. In this regard, of great interest is the class of imidazoline receptor agonists, which not only reduce sympathetic activity and blood pressure (BP), but also have a positive effect on insulin resistance, lipid and glucose metabolism [6,7]. However, the influence of treatment with moxonidine on the functional activity of the sympathetic-adrenal system studied, not studied and the processes of lipid peroxidation on the background of treatment with agonists of imidazoline receptors. On this basis, undertaken the present study

Effect of Metformin Combined with Losartan on Vascular Endothelial Growth Factor and Angiotensin II in Serum of Spontaneously Hypertensive Rats

To investigate the effects of metformin combined with losartan on vascular endothelial growth factor and angiotensin II in serum of spontaneously hypertensive rats, 30 spontaneously hypertensive rats were divided into 3 groups according to different treatment methods. The spontaneously hypertensive rats group was administered was without drug intervention. The metformin group was given orally normal saline mixed with metformin tablets. The combination group received the losartan potassium tablets in addition to metformin. The treatment time was 3 w and the expression of vascular endothelial growth factor and angiotensin II in serum was measured. Rats were sacrificed, the brain tissues were taken, the vascular endothelial growth factor and angiotensin II in the brain tissue were detected by immunohistochemistry and immune blotting expression. Before treatment, the blood pressure of rats in the three groups was similar (p>0.05). Compared to the blood pressure before treatment, the blood pressure of rats in metformin group and combined group decreased significantly (p 0.05). After treatment the levels of vascular endothelial growth factor and Angiotensin II in metformin group and combination group decreased (p<0.05). After treatment, the expression of vascular endothelial growth factor and angiotensin II in metformin group was lower than that in spontaneously hypertensive rats group. The expression of angiotensin II in brain tissue of metformin group was less than that of spontaneously hypertensive rats group (p<0.05), and that of the combined group was less than that of metformin group (p<0.05). Combined use in the treatment of spontaneous hypertension has a good antihypertensive effect, and serum and brain tissue vascular endothelial growth factor and angiotensin II were significantly decreased, improving the condition.

Preservative-free fixed combination in the treatment of open-angle glaucoma and ocular hypertension: the VISIONARY Study (EUPAS22204)

To evaluate efficacy, tolerability, and safety of PF tafluprost/timolol FC in patients with primary open-angle glaucoma (POAG) and ocular hypertension (OH) who couldn't tolerate or gave insufficient response to topical beta-adrenoblockers or prostaglandin analogue monotherapy. The prospective multicenter European VISIONARY study (EUPAS22204) included 87 patients from 7 ophthalmological centers in Russia with mean age of 63.9±11.8. Primary endpoint was mean IOP change at month 6. The patients were monitored for changes in in the severity of ocular signs and symptoms. Statistically significant (p<0.0001) reduction of mean IOP from baseline was seen at all study visits: 7.3±5.17 mmHg at week 4, 7.4±5.40 mmHg at week 12, and 7.1±5.10 mmHg at month 6. By month 6, IOP has decreased by 20; 25; 30 and 35% from baseline in 77.0%, 58.9%, 43.7%, and 31.0% of study patients, respectively. Conjunctival hyperemia was significantly reduced at all study visits. Significant reductions in dry eye symptoms (p<0.0010), irritation (p=0.0204) and itching (p=0.0010) were also observed. After 6 months on PF tafluprost/timolol FC, 85.7% of patients described it as easy or very easy to tolerate. In clinical practice, PF tafluprost/timolol FC provided statistically significant IOP reductions in patients with POAG and OH insufficiently controlled by or intolerant to monotherapy with topical beta-adrenoblockers or a prostaglandin analogue. The highest IOP reduction was seen at week 4 and was maintained over the 6-month study period. There was also a decrease in the severity of symptoms of ocular surface condition.

ACE inhibitory activity in vitro and antihypertensive effect in vivo of LSGYGP and its transepithelial transport by Caco-2 cell monolayer

• The IC 50 value of ACEI activity of LSGYGP in vitro was 25.74 μM. • The ACEI kinetic of LSGYGP was noncompetitive. • LSGYGP had a high binding affinity with ACE sites by seven short hydrogen bonds. • LSGYGP had a good antihypertensive effect in vivo and lung was a key target tissue. • LSGYGP could be absorbed by Caco-2 cell monolayer, and partly degraded or modified. Leu-Ser-Gly-Tyr-Gly-Pro (LSGYGP) was obtained in our previous study. The angiotensin I-converting enzyme inhibitory (ACEI) activity in vitro and the antihypertensive effect in vivo of LSGYGP were determined in this study. The IC 50 value of ACEI activity of LSGYGP was 25.74 μM, and the ACEI kinetic was noncompetitive. LSGYGP showed a high binding affinity with ACE sites by using seven short hydrogen bonds. LSGYGP had a clear antihypertensive effect on spontaneously hypertensive rats, and the systolic blood and diastolic blood pressures remarkably decreased by 19.81% and 29.92% in 3 h of administration. The ACE activities of serum, kidneys, and lungs were determined at different times, and lung was evaluated as the key target tissue. LSGYGP was completely absorbed by Caco-2 cell monolayer, and the transport degree was 3.5%. Furthermore, several degradations and modifications of LSGYGP, such as SGYGP, LSGY, GYGP, LSGYP, LSSGYGP, and LSLSGYGP, were found during the transport process.

Study on the Antihypertensive Mechanism of Astragalus membranaceus and Salvia miltiorrhiza Based on Intestinal Flora-Host Metabolism.

Our previous studies have shown that the combination of Astragalus membranaceus and Salvia miltiorrhiza (HD) had a good antihypertensive effect, but its potential mechanism remained unclear. This study aimed to investigate the role of intestinal flora and serum metabolism induced by HD against hypertension. 16 spontaneous hypertensive rats (SHRs) were divided into HD group (5.9 g/kg) and model group (M) (normal saline), with eight Wistar-Kyoto (WKY) rats as control group (W) (normal saline). Rats were fed by gavage once a day for 28 days. The changes of intestinal flora and serum metabolism were analyzed by 16S rDNA sequencing and LC-MS/MS assay. HD decreased blood pressure steadily, improved the structure and composition of imbalance flora in SHRs, increased the abundance and diversity of flora, and decreased flora Firmicutes to Bacteroidetes (F/B) ratio. Rumen bacterium NK4A214, Clostridium sp. MC 40 increased remarkably in M group. Akkermansia, Akkermansia muciniphila, and Lactobacillus intestinalis increased significantly in HD group, which were functionally related to the significant increase of Lachnoclostridium, Faecalibaculum, and Lactobacillus reuteri in W group, which were all probiotics producing butyric acid, lactic acid, and regulating inflammation and other antihypertensive related factors. HD also changed the serum metabolic pattern of SHRs. 16 potential biomarkers related to inflammation, vasodilation, steroid hormones, oxidative stress, and etc. changed significantly, mainly enriched in arachidonic acid metabolism, tryptophan metabolism, steroid hormone biosynthesis, and glutathione metabolism. The correlation analysis demonstrated that the dominant genius and species in three groups were highly correlated with steroid hormone biosynthesis, arachidonic acid metabolism, tryptophan metabolism, and vitamin B6 metabolism. Our research indicated that HD had a good antihypertensive effect, which may be driven by the protective intestinal flora and beneficial metabolites induced by it, and the metabolites were closely related to the changes of intestinal flora. It provided new insights for the antihypertensive mechanism of HD.

Prophylactic Effects of Polymethoxyflavone-Rich Orange Peel Oil on Nω-Nitro-L-Arginine-Induced Hypertensive Rats

The prophylactic effects of the polymethoxyflavones (PMFs) in long-leaf orange peel oil (OPO) were determined using an Nω-nitro-L-arginine-induced hypertensive rat model. The OPO contained eight PMF components, namely sinensetin, hexamethoxyflavone, tetramethyl-O-isoscutellarein, nobiletin, tetramethyl-O-scutellarein, heptamethoxyflavone, 5-demethylnobiletin and tangeretin. After treatment with OPO, the SP (systolic pressure) and DP (diastolic pressure) in hypertensive rats were reduced. The NO (nitric oxide) contents in serum, heart, liver and kidney of OPO-treated Nω-nitro-L-arginine (L-NNA)-induced hypertensive rats were higher than those in untreated hypertensive rats, but the MDA (malondialdehyde) contents in OPO-treated rats were lower than those of the control rats (untreated hypertensive rats). ET-1 (endothelin-1), VEGF (vascular endothelial growth factor) and E-selectin serum levels in hypertensive rats could be reduced, but the CGRP (calcium gene-related peptide) level could be increased by OPO treatment. The results of the qPCR assay showed that OPO upregulated HO-1 (heme oxygenase-1), nNOS (neuronal nitric oxide synthase) and eNOS (endothelial nitric oxide synthase) mRNA expression and downregulated ADM (adrenomedullin), RAMP2 (receptor activity modifying protein 2) and iNOS (inducible nitric oxide synthase) expression in hypertensive rats. The Western blot results also proved that OPO upregulated nNOS and eNOS protein expression and downregulated iNOS expression in hypertensive rats. Based on this study, we could conclude that OPO showed good antihypertensive effects, and the effect was concentration dependent.

Screening, discovery, and characterization of angiotensin-I converting enzyme inhibitory peptides derived from proteolytic hydrolysate of bitter melon seed proteins

In this study, new angiotensin-I converting enzyme (ACE) inhibitory peptides were comprehensively identified from a thermolysin digest of bitter melon (Momordica charantia) seed proteins. The hydrolysate was fractionated by reversed-phase high performance liquid chromatography (RP-HPLC), and the inhibitory activities of the resulting fractions were evaluated using ACE inhibitory assay. Two novel ACE inhibitory peptides (VY-7 and VG-8) were identified using liquid chromatography-tandem mass spectrometry (LC-MS/MS) and database-assisted peptide sequencing. VY-7 and VG-8 were derived from momordin A and MAP30, respectively, and their IC50 values were as low as 8.64±0.60 and 13.30±0.62μM, respectively. Lineweaver–Burk plots further indicated that VY-7, which showed the best IC50 value, acts as a competitive inhibitor. Notably, the content of VY-7 in crude thermolysin digest was determined to be as high as 14.89±0.88μg/mg using LC-MS/MS quantification. In the spontaneously hypertensive rat (SHR) model, oral administration of VY-7 at 2mg/kg body weight significantly decreased the systolic blood pressure. The interaction between VY-7 and ACE was examined using molecular docking calculations and the results suggested that certain residues of VY-7 can fit perfectly into the S1, S1’ and S2’ regions of the binding pocket of ACE. Biological significanceOne of the most common supportive therapies for treating hypertension is the use of synthetic drugs to inhibit ACE activity. Synthetic ACE inhibitors possess good antihypertensive effects, but come with accompanying side effects. Therefore, food-derived ACE inhibitory peptides are regarded as safer alternatives and are attracting much attention for hypertension treatment. In this study, we comprehensively identified peptides derived from bitter melon (Momordica charantia) seed proteins (BMSPs) using a shotgun proteomics approach. Based on results from an in vitro ACE inhibitory assay, two peptides (VY-7 and VG-8) derived from momordin A and MAP30 proteins, respectively, showed good ACE inhibitory activities. For VY-7, which showed the best IC50 value (8.64±0.60μM), the inhibition type was determined to be competitive inhibition, as found using a Lineweaver–Burk plot. The novel ACE inhibitory peptide VY-7 (at 2mg/kg body weight) as well as the crude hydrolysate of BMSPs (at 10mg/kg body weight) showed significant and moderate antihypertensive effects, respectively, in an animal model of hypertension, spontaneously hypertensive rats (SHRs). The present work demonstrated the screening of ACE inhibitory peptides from BMSPs and, as far as we know, VY-7 is the first well-characterized antihypertensive peptide derived from bitter melon seeds.

A Novel ACE Inhibitory Peptide Ala-His-Leu-Leu Lowering Blood Pressure in Spontaneously Hypertensive Rats.

Ala-His-Leu-Leu (AHLL) was isolated and purified from the loach (Misgurnus anguillicaudatus) hydrolysate in our previous study. The aim of this study was to investigate the antihypertensive effects of angiotensin-I-converting enzyme (ACE) inhibitory peptide AHLL in spontaneously hypertensive rats (SHRs). AHLL showed good antihypertensive effects in SHRs during the long-term oral administration and no allergic reactions or coughing were observed. After 2 months of oral administration of AHLL, the body weight growth was normal. The decrements in systolic blood pressure of the high dose (5 mg/kg bw) and the low dose of AHLL (1 mg/kg bw) treatment groups were 22.1 and 5.0 mmHg at week 8, respectively. Compared to the control group, the concentrations of triglyceride and sodium in serum were reduced significantly in the high-dose group after 2 months. The ACE activity of kidney and lung decreased significantly, which indicated that AHLL exerted an antihypertensive effect on kidney and lung and they were the target sites of AHLL. These results strongly supported the in vivo antihypertensive mechanism of AHLL.

Patients with arterial hypertension associated with metabolic disorders: characteristics and therapeutic approach

Arterial hypertension (AH) is associated with metabolic disorders in approximately 80% of cases. There is a pandemic of so-called new risk factors, such as insulin resistance and association with systemic type of hyperinsulinemia, abdominal obesity, hyperinsulinemia and a special type of dislipidemy, nowadays. Patients with AH associated with such metabolic disorders are at a higher risk of developing cardiovascular disease and diabetes. However, it is very difficult to achieve the target level of blood pressure in this category of patients. Usually, these patients should be treated using combination therapy at the beginning of the treatment. Drugs, which possess good antihypertensive effect, as well as an additional positive influence on metabolic parameters, for instance I2-imidazoline receptor agonists, can be used as the drugs of choice in combination with ACE inhibitorsor angiotensin II receptor blockersin this category of patients.

The clinical observation of 55 hypertension patients treated with candesartan capsule

Objective To explore the treatment effect of candesartan capsule in the treatment of hypertension, and to provide evidence for clinical treatment of hypertension patients. Methods 133 patients with hypertension were randomly divided into the observation group and the control group. 64 cases in the control group were given captopril, 69 cases in observation group were given candesartan capsule on the basis of the control group. The treatment outcome after a period of treatment, the average treatment effect and adverse reaction of SBP and DBP were observed. Results The total effective rate of the observation group was 98.55% (68/69), which was significantly higher than 90.62%(58/64) of the control group(χ2= 6.22,P 0.05). Conclusion Candesartan capsule in the treatment of hypertension has good antihypertensive effect, and has no adverse reaction of antihypertensive drugs. Key words: Candesartan; Hypertension; Curative effect

CALCIUM ANTAGONISTS IN ARTERIAL HYPERTENSION TREATMENT: SPECIFICS OF LERCANIDIPINE

Lercanidipine is a dihydropyridine calcium antagonist of the 3rd generation, with high level of vasoselectivity, long lasting effect and good antihypertensive effectiveness. The review shows the main specifics of pharmacokinetics and mechanism of action of the drug. It is known that lercanidipine supports renoprotection, left ventricle hypertrophy reduction, improvement of elastic properties of the vessels and central blood pressure decrease. Sympathetic activation in lercanidipine is almost absent, that makes up its good tolerability and improves patients’ compliance.

THE EFFECTIVENESS OF LERCANIDIPINE IN REDUCING THE RISK OF ARTERIAL HYPERTENSION COMPLICATIONS

Despite progress in reducing the risk of hypertension (HT) complications, control of blood pressure (BP) levels remains inadequate. Dihydropyridine calcium channel blockers show antihypertensive effect due to significant vasoselective action with a minimal impact on a conductive system of the heart. Lercanidipine is a dihydropyridine calcium channel blocker of the third generation with high lipophilicity and long-lasting action. Lercanidipine had shown both in monotherapy and in combination with ACE inhibitors or angiotensin II blockers the good antihypertensive effect with stable BP profile throughout the day, organoprotection that slowed down the progression of HT complications, metabolic neutrality and safety in mild to moderate HT.

Артериальная гипертония у больных с метаболическими нарушениями: особенности и тактика лечения

Arterial hypertension (AH) is associated with metabolic disorders in approximately 80% of cases. There is a pandemic of so-called new risk factors, such as insulin resistance and association with systemic type of hyperinsulinemia, abdominal obesity, hyperinsulinemia and a special type of dislipidemy, nowadays. Patients with AH associated with such metabolic disorders are at a higher risk of developing cardiovascular disease and diabetes. However, it is very difficult to achieve the target level of blood pressure in this category of patients. Usually, these patients should be treated using combination therapy at the beginning of the treatment. Drugs, which possess good antihypertensive effect, as well as an additional positive influence on metabolic parameters, for instance I2-imidazoline receptor agonists, can be used as the drugs of choice in combination with ACE inhibitorsor angiotensin II receptor blockersin this category of patients.

COMBINATION THERAPY IN THE MANAGEMENT OF ARTERIAL HYPERTENSION: EFFECTIVENESS OF THE LERCANIDIPINE AND ENALAPRIL COMBINATION

This review presents the evidence on the benefits of fixed-dose combination therapy for arterial hypertension management. The focus is on the combination of a third-generation dihydropyridine calcium antagonist lercanidipine and an ACE inhibitor enalapril. Lercanidipine is characterised by high vascular selectivity and lipophilicity, good antihypertensive effectiveness, and prolonged, gradually developing therapeutic effects. Literature data on the effectiveness of the lercanidipine-enalapril combination are presented. This combination facilitates a marked reduction in blood pressure levels, which is particularly relevant for elderly patients and patients with diabetes mellitus or obesity. The combination of pharmacologic effects of lercanidipine and enalapril provides additional benefits in terms of organ protection and reduction of adverse effects of the antihypertensive treatment.

Effects of benazepril on inflammatory cytokines in patients with primary hypertension

Objective To investigate the effects of Benazepril on inflammatory cytokines in patients with primary hypertension and its efficacy analysis.Methods 72 patients with mild to moderate primary hypertension were randomly divided into benazepril group(37 cases)and control group(35 cases).The control group patients were given felodipine sustained release tablets Stag,1 times daily.Benazepril group were given benazepril tablets 10mg,1 times daily.Both groups were treated for 8 weeks.Changes in blood pressure and heart rate,plasma inflammatory cytokine levels and the adverse reactions were observed.Results After 8 weeks of treatment,the patients' blood pressures were significantly decreased (t =2.87,2.43,2.31,2.23,P ＜ 0.05 or P ＜ 0.01) than before in both groups.And the decrease in the benazepril group was more obvious than that in the control group (t =2.21,2.13,all P ＜ 0.05),while the patients' heart rates in the two groups showed no significant change (P ＞ 0.05) ; Patients' plasma IL-4 and IL-8 levels decreased significantly,plasma IL-10 levels increased significantly (t =2.99,2.87,3.21,2.13,2.19,2.23,all P＜0.05 or P＜0.01),and the magnitude of decrease or increase in the benazepril group were more obvious compared with the control group (t =2.21,2.13,2.34,all P ＜ 0.05).Conclusion Benazepril in the treatment of primary hypertension has good antihypertensive effect and security which can significantly reduce the plasma levels of proinflammatory cytokines IL-4 and IL-8 levels,improve the anti-inflammatory cytokine IL-10 levels,and has the role of suppressing the inflammatory response of the vessel wall. Key words: Hypertension; Cytokines ; Benazepril

Эффективность моксонидина в лечении артериальной гипертензии у больных с метаболическим синдромом

Цель исследования: оценить антигипертензивную и органопротективную эффективность моксонидина и его влияние на липидный и углеводный обмен у больных с артериальной гипертензией (АГ) и метаболическим синдромом (МС).Материалы и методы исследования. В исследование были включены 46 мужчин с АГ 1–2-й ст. и МС. МС устанавливали согласно критериям IDF (2005). Всем больным проводились ЭхоКГ, тест с реактивной гиперемией, пероральный тест толерантности к глюкозе, определение толщины комплекса интима-медиа (КИМ), липидов, инсулина и мочевой кислоты крови. Все больные принимали моксонидин в дозе 0,4 мг/сут в течение 12 недель.Результаты исследования. На фоне монотерапии моксонидином достигнут хороший антигипертензивный эффект: степень снижения ΔСАД составила –11,7 ± 4,4 %, ΔДАД — –13,4 ± 5,9 %. 69,5 % больных достигли целевых значений АД. На фоне 3-месячной терапии отмечалась достоверная регрессия гипертрофии левого желудочка (ЛЖ) и улучшение диастолической функции ЛЖ. Также отмечалось достоверное уменьшение толщины КИМ сонной артерии, улучшение эндотелийзависимой вазодилатации (ЭЗВД) на фоне 12-недельной монотерапии моксонидином. Анализ липидного спектра показал, что отмечалось достоверное снижение уровня общего холестерина и тиреоглобулина. Применение моксонидина приводило к достоверному снижению уровня инсулина, что сопровождалось достоверным снижением индекса НОМА. На фоне монотерапии моксонидином отмечалось достоверное снижение уровня мочевой кислоты.Заключение. Монотерапия моксонидином оказывает хороший антигипертензивный эффект и способствует регрессии гипертрофии ЛЖ, улучшению диастолической функции ЛЖ и ЭЗВД, снижает инсулинорезистентность у больных с АГ и МС.