Significant Antihypertensive Effect Research Articles

Effects of olive leaf extract and nifedipine, alone and in combination, on blood pressure, neutrophil gelatinase-associated lipocalin, malondialdehyde, and creatinine levels in an Nω-nitro-L-arginine methyl ester-induced rat model of preeclampsia

Preeclampsia (PE) is a significant health problem in pregnancy, affecting 6–7% of all gestations and leading to fetal growth retardation, infant morbidity and mortality, premature birth, and maternal death. Currently, effective treatment options for PE are limited. This study aimed to evaluate the therapeutic potential of olive leaf extract (OLE) and nifedipine, alone and in combination, in improving pregnancy outcomes in rats induced with Nω-nitro-L-arginine methyl ester hydrochloride (L-NAME). Rats were treated with single and combination treatments of nifedipine and OLE for four weeks, after being induced with L-NAME for six weeks. Following gestational day assessment and systolic blood pressure testing, the rats were sacrificed, and blood samples were collected for Neutrophil Gelatinase-Associated Lipocalin (NGAL), Malondialdehyde (MDA), proteinuria and Creatinine (SCr) Levels examinations. The results revealed the combination of nifedipine and OLE significantly improved the results of several biomarker analyses associated with PE, including increased NGAL levels, a significant decrease in MDA levels, decrease in proteinuria and elevated creatinine levels. The combination nifedipine and OLE treatment also exhibited a significant antihypertensive effect compared to either nifedipine or OLE monotherapy, as evidenced by the reduction in systolic and diastolic blood pressure levels. This study provides novel evidence for the potential of olive leaf extract as a nutraceutical adjunct for the prevention and treatment of PE. The significant improvements observed in several pathological features associated with PE, including antihypertensive effects, warrant further investigation. Future research should focus on elucidating the underlying mechanisms of action and exploring the clinical applicability of olive leaf extract in human populations with PE.

Mechanism and functional substances of Saiga antelope horn in treating hypertension with liver-yang hyperactivity syndrome explored using network pharmacology and metabolomics

Ethnopharmacological relevanceSaiga antelope horn (SAH) is a traditional Chinese medicine for treating hypertension with liver-yang hyperactivity syndrome (Gan-Yang-Shang-Kang, GYSK), that has a long history of clinical application and precise efficacy, but its mechanism and functional substances are still unknown. Based on the demand for alternative research on the rare and endangered SAH, the group designed and carried out the following studies. Aim of the studyThe purpose of this research was to demonstrate the functional substances and mechanisms of SAH in the treatment of GYSK hypertension. Materials and methodsThe GYSK-SHR model was constructed by administering a decoction of aconite to spontaneously hypertensive rats (SHRs). Blood pressure (BP), behavioural tests related to GYSK, and pathological changes in the kidneys, heart and aorta were measured to investigate the effects of SAH on GYSK-SHRs. Proteomic analysis was used to identify the keratins and peptides of SAH. Moreover, network pharmacology and plasma metabolomics studies were carried out to reveal the mechanisms by which functional peptides in SAH regulate GYSK-hypertension. ResultsSAH has a significant antihypertensive effect on GYSK hypertensive animals. It has also been proven to be effective in protecting the function and structural integrity of the kidneys, heart and aorta. Moreover, SAH improved the abnormalities of 31 plasma biomarkers in rats. By constructing a “biomarker-target-peptide” network, 10 functional peptides and two key targets were screened for antihypertensive effects of SAH. The results indicated that SAH may exert a therapeutic effect by re-establishing the imbalance of renin-angiotensin (RAS) system. ConclusionsFunctional peptides from keratin contained in SAH are the main material basis for the treatment of GYSK-hypertension and exhibited the protective effect on the GYSK-SHR model through the RAS system.

N-phenyl and N-benzyl substituted succinimides: Preclinical evaluation for their antihypertensive effect and underlying mechanism

The study was designed to investigate the antihypertensive potential of 2-(2, 5-dioxo-1-phenylpyrrolidin-3-yl)-3-(4-isopropylphenyl)-2-methylpropanal (Comp-1) and 2-(1-benzyl-2,5-dioxopyrrolidin-3-yl)-3-(4-isopropylphenyl)-2-methylpropanal (Succ-5) in rats. The study results showed that, just like nifedipine (the standard reference drug), the test compounds, Comp-1 (at doses of 15 and 20 mg/kg) and Succ-5 (at a dose of 20 mg/kg) had significant antihypertensive effect against deoxycorticosterone acetate-salted rats. The test compounds maintained the level of cardiac markers troponin I and creatinine kinase myocardial bands (CK-MB) in serum, and modulate the oxidative stress markers Glutathione s-transferase (GST) activity, reduced glutathione (GSH), catalase levels, and lipid peroxidation (LPO). These compounds also reduced the expression of inflammatory markers, including cyclooxygenase-2 (COX-2) and tumor necrosis factor alpha (TNF-α) in heart tissues. Furthermore, in the ex-vivo study, the test substances relaxed the contractions induced by phenylephrine (PE) and potassium (K+). Vasodilation was endothelium-independent because the test substances showed nearly the same effect in aortic rings with intact endothelium, denuded endothelium, and with L-NAME pretreatment. The test compounds shifted the calcium curve to the right, i.e., contraction was inhibited and decreased the maximal response. This study demonstrated the antihypertensive, anti-inflammatory, antioxidant, and vasodilate effects of the test compounds. In addition, the results supported the phenomenon of calcium channel blockades responsible for vasodilation.

A comprehensive in vivo study of the antihypertensive properties and toxicity of roselle (Hibiscus sabdariffa L.)

Background: Roselle (Hibiscus sabdariffa L.) calyces have been used in traditional medicine as diuretics, mild laxatives, and antihypertensive agents but to date, a comprehensive study of its pharmacological activity and safety has not been conducted. Aims of the study: The current study aims to provide a comprehensive evaluation of the antihypertensive efficacy and toxicity profile of Roselle (H. sabdariffa L.) calyces extract. Utilizing animal models, the investigation assessed the dose-dependent pharmacological effects and safety of H. sabdariffa L. Results: The findings indicate that the extract exerts a significant antihypertensive effect at a dose of 250 mg/kg body weight (BW), lowering systolic and diastolic blood pressures by 10.12% and 11.63%, respectively. Ethyl acetate fractions administered at 112.5 mg/kg BW demonstrated greater efficacy than n-hexane and aqueous fractions, suggesting that the active compounds likely possess semi-polar properties. Acute toxicity testing yielded an LD50 of 8.75 g/kg BW for male rats and 7.5 g/kg BW for female rats, classifying the extract as slightly toxic. The sub-chronic toxicity study shows that H. sabdariffa L. demonstrates an effect on bodyweight and urea levels in male and female rats, while the change in the blood parameters, creatinine level, and the liver index was only observed in female rats. Conclusions: These data suggest that H. sabdariffa L. extract exhibits therapeutic promise but should be administered cautiously, preferably at doses lower than 250 mg/kg BW, due to potential toxicity.

The hydroxamic acid derivative YPX-C-05 alleviates hypertension and vascular dysfunction through the PI3K/Akt/eNOS pathway

Hypertension is a prevalent cardiovascular disease characterized by elevated blood pressure and increased vascular resistance. HDAC inhibitors have emerged as potential therapeutic agents due to their ability to modulate gene expression and cellular processes. YPX-C-05, a novel hydroxamic acid-based HDAC inhibitor, shows promise in its vasodilatory effects and potential targets for hypertension treatment. In this study, we aimed to elucidate the mechanisms underlying YPX-C-05's vasodilatory effects and explore its therapeutic potential in hypertension. To determine the ex vivo vasodilatory effects of YPX-C-05, isolated aortic rings precontracted with phenylephrine were used. We assessed YPX-C-05's inhibitory effects on HDACs and its impact on histone H4 deacetylation levels in endothelial cells. Network pharmacology analysis was employed to predict putative targets of YPX-C-05 for hypertension treatment. To investigate the involvement of the PI3K/Akt/eNOS pathway, we employed enzyme-linked immunosorbent assay and to assess the levels of NO, ET-1, BH2, and BH4 in human umbilical vein endothelial cells. And we also analyzed the mRNA expression of eNOS and ET-1. Furthermore, Western blotting was conducted to quantify the phosphorylated and total Akt and eNOS levels in human umbilical vein endothelial cell lysates following treatment with YPX-C-05. In order to elucidate the vasodilatory mechanism of YPX-C-05, we employed pharmacological inhibitors for evaluation purposes. Furthermore, we evaluated the chronic antihypertensive effects of YPX-C-05 on N-omega-nitro-L-arginine-induced hypertensive mice in an in vivo model. Vascular remodeling was assessed through histological analysis. Our findings demonstrated that YPX-C-05 exerts significant vasodilatory effects in isolated aortic rings precontracted with phenylephrine. Furthermore, YPX-C-05 exhibited inhibitory effects on HDACs and increased histone H4 acetylation in endothelial cells. Network pharmacology analysis predicted YPX-C-05 might activate endothelial eNOS via PI3K/Akt signaling pathway. Inhibition of the PI3K/Akt/eNOS pathway attenuated the vasodilatory effects of YPX-C-05, as evidenced by reduced levels of phosphorylated Akt and eNOS in human umbilical vein endothelial cell lysates. The chronic administration of YPX-C-05 in N-omega-nitro-L-arginine-induced hypertensive mice resulted in significant antihypertensive effects. Histological analysis demonstrated a reduction in vascular remodeling, further supporting the therapeutic potential of YPX-C-05 in hypertension. This study demonstrates for the first time that the novel hydroxamic acid-based HDAC inhibitor YPX-C-05 produces significant antihypertensive and vasodilatory effects through the PI3K/Akt/eNOS pathway. Our findings support the developing prospect of YPX-C-05 as a novel antihypertensive drug.

Vasorelaxant and Antihypertensive Effects of (3β)-ursen-12-en-3,28-diol by NO/cGMP System

Objective: The aim of this study was to determine the vasorelaxant effect of semisynthetic derivatives of ursolic acid, establish the mode of action, and determine the antihypertensive effect of the most active compound. Methods: Isolated aorta rat rings (ex vivo assay), with and without endothelium, were used to determine the vasorelaxant effect of seven semisynthetic derivatives of ursolic acid (UA-01 to UA-07). Then, the effect of the most active compound was studied in ex vivo assay using L-NAME, ODQ and indomethacin to determine its mode action. Finally, the in vivo cardiovascular effect and molecular docking of the most active compound were determined. Results: UA-07 was the most potent compound of the derivatives, since UA-07 induced significant relaxant effect in concentration- and endothelium-dependent manners (Emax = 79.09% and EC50 = 110 μM) on aortic rat rings pre-contracted with noradrenaline (NA, 0.1 μM). Also, endothelium-derived nitric oxide seems to be involved in the mechanism of action of UA-07, because pre-incubation with L-NAME (a NOS inhibitor) and ODQ (a soluble guanylate cyclase inhibitor) significantly reduced its vasorelaxant effect. Further, UA-07 showed a similar binding affinity as ursolic acid on eNOS C1 binding pocket in in silico studies. Finally, treatment with UA-07 (50 mg/Kg) on spontaneously hypertensive rats (SHR) significantly decreased diastolic blood pressure for seven hours. Conclusion: These results demonstrate the significant antihypertensive effect of UA-07, possibly through the NO/cGMP system.

Effect of renal denervation on diastolic function in patients with resistant hypertension and type 2 diabetes mellitus

Aim: To assess the change in the left ventricular (LV) diastolic function (DF) in patients with resistant hypertension (RHTN) and type 2 diabetes mellitus (T2DM) during 6-month follow-up after renal denervation (RDN) according to echocardiography in conjunction with changes in hemodynamic parameters.Material and Methods. A single center prospective interventional study with renal denervation included 30 patients with RHTN and T2DM. All patients underwent measurement of office and 24-hour blood pressure (BP), echocardiography according to the standard method with an assessment of LV DF.Results. At 6 months after RDN, a significant antihypertensive effect was noted (p < 0.05), as well as an improvement in LV DF in the form of a decrease in E/e` by 1 c.u. was observed in 50% (15) patients. A significant decrease in the average E/e` was documented (–1.3 [95% CI –2.55; –0.08], р = 0.038). There were no changes in the indexed volumes of the left atrium (р = 0.940). The baseline values of E/e` had correlation with the level of mean pulse BP 24h (r = 0.51, р = 0.001) in the absence of significant relationships with other ABPM parameters. A decrease in systolic BP 24h by 3 mm Hg and an increase in nocturnal systolic BP fall by 1.6% were accompanied by a decrease in the average E/e` by 1 unit. According to the ROC-analysis, baseline level of nocturnal systolic BP fall 5.5% or less associated with a decrease in the E/e` ratio by more than 1 unit.Conclusion. Renal denervation in patients with RHTN and T2DM is accompanied by a favorable effect on LV diastolic function during 6-month follow-up, closely related to the hemodynamic effects of the procedure such as a decrease in systolic and pulse BP 24h, as well as improvement in the circadian rhythm of BP.

LC-MS Fingerprinting Development for Standardized Precipitate from Agastache mexicana, Which Induces Antihypertensive Effect through NO Production and Calcium Channel Blockade.

The aim of this work was to evaluate the vasorelaxant and antihypertensive effects of a standardized precipitate of the hydroalcoholic extract from Agastache mexicana (PPAm), comprising ursolic acid, oleanolic acid, acacetin, luteolin and tilianin, among others. In the ex vivo experiments, preincubation with L-NAME (nonspecific inhibitor of nitric oxide synthases) reduced the relaxation induced by PPAm; nevertheless, preincubation with indomethacin (nonspecific inhibitor of cyclooxygenases) did not generate any change in the vasorelaxation, and an opposed effect was observed to the contraction generated by CaCl2 addition. Oral administration of 100 mg/kg of PPAm induced a significant acute decrease in diastolic (DBP) and systolic (SBP) blood pressure in spontaneously hypertensive rats, without changes in heart rate. Additionally, PPAm showed a sustained antihypertensive subacute effect on both DBP and SBP for 10 days compared to the control group. On the other hand, human umbilical vein cells treated with 10 µg/mL of PPAm showed a significant reduction (p < 0.05) in intracellular adhesion molecule-1, compared to the control, but not on vascular cell adhesion molecule-1. In conclusion, PPAm induces a significant antihypertensive effect in acute- and subacute-period treatments, due to its direct vasorelaxant action on rat aortic rings through NO production and Ca2+ channel blockade.

Experience of sacubitril/valsartan therapy in hypertension

The aim of the review was to analyze the antihypertensive efficacy and safety of sacubitril/valsartan combination, a representative of a new class of angiotensin receptor-neprilysin inhibitors (ARNIs), in patients with hypertension (HTN) according to clinical trials, including randomized, and meta-analyses. Randomized clinical trials conducted in different age, ethnic and clinical cohorts of HTN patients, as well as meta-analyses showed a more significant antihypertensive effect of sacubitril/valsartan compared with monotherapy with angiotensin II receptor blockers, confirmed by office blood pressure (BP) and 24-hour BP monitoring. At grade 1-2 HTN, sacubitril/valsartan showed greater reduction in systolic and diastolic blood pressure by ~5/2 mm Hg compared to valsartan or olmesartan according to 8-12-week studies. A dose-dependent effect of sacubitril/valsartan was established. A favorable experience was obtained with sacubitril/ valsartan use in various clinical variants of HTN (refractory HTN, isolated systolic HTN in the elderly, HTN in combination with heart failure, with chronic kidney disease), as well as the successful use of sac/vals in combination with other antihypertensive drugs. In long-term studies (52 weeks) in elderly patients with HTN, the positive effects of sacubitril/valsartan in reducing central aortic pressure, systolic blood pressure at night and a decrease in pulse pressure have been shown. Several meta-analyses have shown similar tolerability profiles compared to controls and no increased risk of adverse events.

Maximakinin reduced intracellular Ca2+ level in vascular smooth muscle cells through AMPK/ERK1/2 signaling pathways.

We detect the antihypertensive effects of maximakinin (MK) on renal hypertensive rats (RHRs) and further research the influence of MK on vascular smooth muscle cells (VSMCs) to explore its hypotensive mechanism. The effects of MK on arterial blood pressure were observed in RHRs. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide (MTT) assays were performed to detect the effect of MK on VSMC viability. Western blot and flow cytometry were used to investigate the influence of MK on intracellular Ca2+ levels and protein expression changes in VSMCs. In addition, specific protein inhibitors were applied to confirm the involvement of Ca2+-related signaling pathways induced by MK in VSMCs. MK showed a more significant antihypertensive effect than bradykinin in RHRs. MK significantly decreased intracellular Ca2+ concentrations. Furthermore, MK significantly induced the phosphorylation of signaling molecules, including extracellular signal-regulated kinase 1/2 (ERK1/2), P38, AMP-activated protein kinase (AMPK) and Akt in VSMCs. Moreover, only ERK1/2 inhibitor U0126 and AMPK inhibitor Compound C completely restored the decreased intracellular Ca2+ level induced by MK, and further research demonstrated that AMPK functioned upstream of ERK1/2 following exposure to MK. Finally, HOE-140, an inhibitor of the bradykinin B2 receptors (B2Rs), was applied to investigate the potential targets of MK in VSMCs. HOE-140 significantly blocked the AMPK/ERK1/2 pathway induced by MK, suggesting that the B2Rs might play an important role in MK-induced AMPK and ERK1/2 activation. MK significantly reduces blood pressure in RHRs. MK exerts its antihypertensive effect by activating the B2Rs and downstream AMPK/ERK1/2 pathways, leading to significantly reduced Ca2+ levels in VSMCs.

Orally administered sodium nitrite prevents the increased α-1 adrenergic vasoconstriction induced by hypertension and promotes the S-nitrosylation of calcium/calmodulin-dependent protein kinase II

The unsatisfactory rates of adequate blood pressure control among patients receiving antihypertensive treatment calls for new therapeutic strategies to treat hypertension. Several studies have shown that oral sodium nitrite exerts significant antihypertensive effects, but the mechanisms underlying these effects remain unclear. While these mechanisms may involve nitrite-derived S-nitrosothiols, their implication in important alterations associated with hypertension, such as aberrant α1-adrenergic vasoconstriction, has not yet been investigated. Here, we examined the effects of oral nitrite treatment on vascular responses to the α1-adrenergic agonist phenylephrine in two-kidney, one clip (2K1C) hypertensive rats and investigated the potential underlying mechanisms. Our results show that treatment with oral sodium nitrite decreases blood pressure and prevents the increased α1-adrenergic vasoconstriction in 2K1C hypertensive rats. Interestingly, we found that these effects require vascular protein S-nitrosylation, and to investigate the specific S-nitrosylated proteins we performed an unbiased nitrosoproteomic analysis of vascular smooth muscle cells (VSMCs) treated with the nitrosylating compound S-nitrosoglutathione (GSNO). This analysis revealed that GSNO markedly increases the nitrosylation of calcium/calmodulin-dependent protein kinase II γ (CaMKIIγ), a multifunctional protein that mediates the α1-adrenergic receptor signaling. This result was associated with reduced α1-adrenergic receptor-mediated CaMKIIγ activity in VSMCs. We further tested the relevance of these findings in vivo and found that treatment with oral nitrite increases CaMKIIγ S-nitrosylation and blunts the increased CaMKIIγ activity induced by phenylephrine in rat aortas. Collectively, these results are consistent with the idea that oral sodium nitrite treatment increases vascular protein S-nitrosylation, including CaMKIIγ as a target, which may ultimately prevent the increased α1-adrenergic vasoconstriction induced by hypertension. These mechanisms may help to explain the antihypertensive effects of oral nitrite and hold potential implications in the therapy of hypertension and other cardiovascular diseases associated with abnormal α1-adrenergic vasoconstriction.

Angelica decursiva exerts antihypertensive activity by inhibiting L-type calcium channel

Ethnopharmacological relevanceAngelica decursiva is a perennial herb that belongs to the Umbelliferae family. It is traditionally used to treat fever, upper respiratory tract infections, bleeding and hypertension. However, despite its extensive pharmacological potential, literature reports on its antihypertensive pharmacological properties are scarce. Aim of the studyIn the study, crude extract from A. decursiva roots was examined for its antihypertensive activity and its molecular basis was explored. Materials and methodsA. decursiva roots were extracted with ethanol, and isolated with silica gel normal-phase chromatography and reverse-phase high performance liquid chromatography. L-NAME-induced hypertensive mouse model was used to detect in vivo hypertensive activity. Thoracic aorta ring contraction activity and electrophysiology recordings were employed to evaluate in vitro antihypertensive activity and revealed an antihypertensive target, which was transiently expressed in HEK293T cells. ResultsAngelica decursiva ethanol decoction (ADED) exhibited significant antihypertensive effects in L-NAME-induced hypertension models and phenylephrine-induced vasoconstriction. Further screening revealed that demethylsuberosin is an essential component accounting for the antihypertension effects of A. decursiva. Voltage-gated calcium channel CaV1.2 is the likely target of A. decursiva for its antihypertension effects. ConclusionThe study suggests that A. decursiva and demethylsuberosin may be effective antihypertensive agents in preclinical studies. It appears that A. decursiva and demethylsuberosin exert antihypertensive effects by inhibiting the CaV1.2 channel, which contributes to the vasodilatory effect. The present study provides experimental evidence that A. decursiva is an effective remedy for hypertension in folklore. Demethylsuberosin could be a lead molecule for antihypertension drug development.

Lyophilized hydroalcoholic extract of Passiflora edulis and Zea mays L, as potential arterial hypotension and hypocholesterolemia in hypertensive Mus musculus induced hypertension

The leaves of Zea mays L and Passiflora edulis have multipurpose for conventional medicine for their bioactive compounds, however, their use in animal models lacks demonstration and biomedical valida-tion, hence the objective was to evaluate the effect of lyophilized extract of P. edulis Sims and Z. mays L as a potential arterial hypotensive and induce hypocholesterolemia in hypertensive Swiss albino mice. Forty-eight 8-week-old Swiss albino mice were used by dividing into 4 groups: G1- passion fruit (50 mg [n= 4], 100 mg [n= 4], and 200 mg [n= 4]), G2-purple corn (50 mg [n= 4], 100 mg [n= 4], and 200 mg [n= 4]), and G3-controls: negative control (distilled water [n= 12]), G4-positive control (N-nitro-L-arginine methyl ether (L-NAME) [n= 12]). Mice were fasted to assess systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), glucose and cholesterol at base-line and post induction with L-NAME by indirect method. At 4 weeks of study the animals of G1-passion fruit and G2-purple corn showed significant antihypertensive and hypocholesterolemia effect (p&lt;0.05) resulting the concentration 200 mg as optimal reducer and stabilizer of SBP, DBP, MAP, glucose and cholesterol. In conclusion, the lyophilized extract of P. edulis (passion fruit) and Z. mays L (purple corn) leaves at 200 mg concentration showed excellent antihypertensive and hypocholesterol-emia effects in hypertensive Swiss albino mice.

Emerging topics on renal denervation in hypertension: anatomical and functional aspects of renal nerves.

Inappropriate sympathetic activation is closely associated with the development and progression of hypertension. Renal denervation (RDN) is a neuromodulation therapy performed using an intraarterial catheter in patients with hypertension. Recent randomized sham-operated controlled trials have shown that RDN has significant antihypertensive effects that last for at least 3 years. Based on this evidence, RDN is nearly ready for general clinical application. On the other hand, there are remaining issues to be addressed, including elucidation of the precise antihypertensive mechanisms of RDN, the appropriate endpoint of RDN during the procedure, and the association between reinnervation after RDN and the long-term effects of RDN. This mini review focuses on studies implicating anatomy of the renal nerves, which consist of afferent or efferent and sympathetic or parasympathetic nerves, the response of blood pressure to renal nerve stimulation, and reinnervation of renal nerves after RDN. A comprehensive understanding of the anatomical and functional aspects of the renal nerves and the antihypertensive mechanisms of RDN, including its long-term effects, will enhance our ability to incorporate RDN into strategies to treat hypertension in clinical practice. This mini review focuses on studies implicating anatomy of the renal nerves, which consist of afferent or efferent and sympathetic or parasympathetic nerves, the response of blood pressure to renal nerve stimulation, and reinnervation of renal nerves after renal denervation. Whether the ablation site is sympathetic dominant or parasympathetic dominant, and afferent dominant or efferent dominant, would in turn determine the final output of renal denervation. BP: blood pressure.

Comparative antihypertensive efficacy of combinations of azilsartan medoxomil or olmesartan medoxomil with amlodipine in patients with arterial hypertension, type 2 diabetes mellitus and non-alcoholic fatty liver disease

Оbjective : to compare the effectiveness of the effect of two combination therapy options on office blood pressure (BP), 24-hour blood pressure monitoring (ABPM) and 24-hour BP profile (DAP) in patients with arterial hypertension (AH) associated with type 2 diabetes mellitus (T2D) and non-alcoholic fatty liver disease (NAFLD). Materials and methods: 137 patients with uncontrolled hypertension combined with DM2 and NAFLD were examined. After randomization by the "envelope" method, patients of the 1st group were assigned a combination of azilsartan medoxomil (Az-M) with amlodipine (Aml), the 2nd group a combination of olmesartan medoxomil (Ol-M) with Aml. At baseline, at 4, 8, 12, and 24 weeks, office BP was measured, and ABPM and DAP were analyzed at baseline and at 24 weeks of the study. Results : after 12 weeks in the 1st and 2nd groups, 86,8% and 84,1% of patients, respectively, reached the target level (TA) of blood pressure, which was maintained until the end of the study. After 24 weeks, both groups showed a statistically significant improvement in ABPM parameters and optimization of DAP. At the same time, taking the Ol-M/Aml combination was accompanied by more pronounced positive dynamics of some prognostically important ABPM indicators. Conclusion : despite the significant antihypertensive effect on the background of the use of both combinations, the effect on individual parameters of ABPM Ol-M/Aml was more pronounced.

Calanus oil attenuates isoproterenol-induced cardiac hypertrophy by regulating myocardial remodeling and oxidative stress

ABSTRACT Calanus oil, an oil extracted from the marine crustacean Calanus finmarchicus, is one of the richest sources of omega-3 and poly-unsaturated fatty acids. Although calanus oil has been shown to have a significant anti-hypertensive, anti-inflammatory, anti-fibrotic and anti-obesity effects in various cardiovascular diseases, but little is known about its effect on pathological cardiac hypertrophy. Thus, the present study was carried out to evaluate the therapeutic effect of calanus oil on cardiac hypertrophy. Cardiac hypertrophy was induced by subcutaneous injections with isoproterenol (5 mg/kg b.w) for 14 consecutive days. Calanus oil (400 mg/kg) was given orally for 4 weeks. Cardiac pathological remodeling was evaluated by echocardiography, after which morphometric, biochemical, histological and ultrastructural analyses were performed. Calanus oil treatment significantly ameliorated isoproterenol-induced structural and functional alterations in echocardiography. Calanus oil also reduced the relative heart weight, significantly decreased the elevated cardiac enzymes (LDH and CK-MB) and the lipid peroxidation marker (MDA), augmented the myocardial antioxidant status (TAC), and ameliorated the histopathological and ultrastructural changes in cardiac tissues and prevented interstitial collagen deposition. The present study, for the first time, provided morphometric, biochemical, histological and ultrastructural evidences supporting the promising anti-hypertrophic effect of calanus oil against ISO-induced cardiac hypertrophy. This anti-hypertrophic effect of calanus oil is via regulating myocardial remodeling and oxidative stress. Therefore, it could be used as potential pharmacological intervention in the management of cardiac hypertrophy.

In Vitro and In Vivo Antihypertensive Effect of Milk Fermented with Different Strains of Common Starter Lactic Acid Bacteria.

Currently, functional dairy products pave a promising way for the prophylaxis of essential hypertension, and the search for new strains capable of producing such products is a constant challenge for scientists around the world. In this study, the antihypertensive properties of milk fermented with several strains of traditional yogurt starters (Lactobacillus delbrueckii strains Lb100 and Lb200; Lactococcus lactis strains dlA, AM1 and MA1; Streptococcus thermophilus strains 159 and 16t) and one strain of non-conventional probiotic starter (Lacticaseibacillus paracasei ABK) were assessed. The in vitro assessment using angiotensin-converting enzyme inhibition assay was performed for all fermentation products, and the best performed products were tested in vivo using Spontaneously Hypertensive Rat (SHR) animal model. In addition, for the best performed products the fatty acid (FA) composition and FA-related nutritional indices were determined. As a result, the milk fermented with two strains (Lb. delbrueckii LB100 and Lc. lactis AM1) demonstrated significant antihypertensive effect during both in vitro and in vivo experiments. Moreover, the milk fermented with Lb. delbrueckii Lb100 demonstrated significantly better FA-related nutritional indexes and lowered total cholesterol in SHRs upon regular consumption. The obtained results can be used in the future to develop new starter cultures producing effective functional antihypertensive dairy products.

Continuous positive airway pressure may improve hypertension in patients with obstructive sleep apnea-hypopnea syndrome by inhibiting inflammation and oxidative stress.

The work was designed to investigate the effect of continuous positive airway pressure (CPAP) on hypertension in obstructive sleep apnea-hypopnea syndrome (OSAHS) patients and to elucidate the underlying mechanisms. We examined the effect of CPAP on blood pressure and biomarkers reflecting inflammation and oxidative stress, and investigated the correlation between changes in blood pressure and the biomarkers. CPAP significantly improved clinic, ambulatory and home blood pressure (p < 0.05). The hypotensive effect of CPAP was positively correlated with the decrease of interleukin-6, C-reactive protein, NADPH oxidase and malonaldehyde. CPAP has a significant antihypertensive effect on OSAHS patients, especially nocturnal hypertension, possibly by counteracting inflammation and oxidative stress.

Comparative Peptidomics Analysis of Milk Fermented by Lactobacillus helveticus

Lactobacillus helveticus is one of the commonly used starter cultures for manufacturing various fermented dairy products. However, only a few studies have explored the cleavage region preference of L. helveticus with different cell envelope proteinase (CEP) genes. In the present study, we profiled the peptide composition of milk samples fermented by three different L. helveticus strains by means of peptidomics to illustrate their different proteolysis patterns. The result revealed that the differences in peptide profiles of milk samples fermented by different L. helveticus strains were mainly a result of variations in the peptide patterns of the casein fractions, which were correlated with CEP genotypes. This was mainly reflected in the extensiveness of the hydrolysis region of αS1-casein and the degree of β-casein hydrolysis. Bioactive peptides were mostly derived from the hydrolysis region common to the three L. helveticus strains, and DQHXN-Q32M42 fermentation resulted in the highest diversity and abundance of bioactive peptides and a significant antihypertensive effect in spontaneous hypertension rats.

EFFECT OF DIFFERENT TREATMENT OF HYPERTENSIVE PATIENTS WITH OBSTRUCTIVE SLEEP APNEA ON BLOOD PRESSURE: A NETWORK META-ANALYSIS

Objective: OSA is one of the common causes of secondary hypertension. The antihypertensive treatment include pharmacotherapy and non-pharmacotherapy. However, the effect of different treatment on blood pressure is still unclear. Theaim of this study was to compare the effect of pharmacotherapy and non-pharmacotherapy for obstructive sleep apnea on blood pressure. Design and method: We searched PubMed, EMBASE, Web of Science, Cochrane Library database, China Biology Medicine disc (up to June 1, 2021) to identify the studies that met the inclusion criteria. Two reviewers independently screened literature, extracted data, and assessed the risk of bias. R software was used to perform the meta-analysis. Results: A total of 30 clinical trials involving 3483 patients were included. Angiotensin-Converting Enzyme Inhibitors(ACEI) /Angiotensin receptor blockers(ARB) showed the most significant antihypertensive effects on office systolic blood pressure as compared with placebo (MD = -4.56, 95%CI: -27.53~-1.69). Mineralocorticoid receptor antagonist (MRA) showed the most significant antihypertensive effects on office diastolic blood pressure as compared with placebo (MD = -15.02, 95%CI: -24.35~-5.72). Rankogram also shows the ACEI/ ARB is the best treatment on office systolic blood pressure and MRA is the best treatment on office diastolic blood pressure. Conclusions: For hypertensive patients with obstructive sleep apnea, Renin-angiotensin-aldosterone System inhibitor (RAS-I) may be the optimal antihypertensive treatment.