Antihypertensive effects of whey protein hydrolysate involve reshaping the gut microbiome in spontaneously hypertension rats

Novel angiotensin-converting enzyme(ACE)inhibitory peptides were identified from whey protein hydrolysates(WPH)in vitro in our previous study and the antihypertensive abilities of WPH in vivo were further investigated in the current study.Results indicated that WPH significantly inhibited the development of high blood pressure and tissue injuries caused by hypertension.WPH inhibited ACE activity(20.81%,P<0.01),and reduced renin concentration(P<0.05),thereby reducing systolic blood pressure(SBP)(12.63%,P<0.05)in spontaneously hypertensive rats.The increased Akkermansia,Bacteroides,and Lactobacillus abundance promoted high short chain fatty acid content in feces after WPH intervention.These changes jointly contributed to low blood pressure.The heart weight and cardiomyocyte injuries(hypertrophy and degeneration)were alleviated by WPH.The proteomic results revealed that 19 protein expressions in the heart mainly associated with the wingless/integrated(Wnt)signaling pathway and Apelin signaling pathway were altered after WPH supplementation.Notably,WPH alleviated serum oxidative stress,indicated by the decreased malondialdehyde content(P<0.01),enhanced total antioxidant capacity(P<0.01)and superoxide dismutase activity(P<0.01).The current study suggests that WPH exhibit promising antihypertensive abilities in vivo and could be a potential alternative for antihypertensive dietary supplements.

Is medical management useful in Moyamoya disease?

Moyamoya disease(MMD),characterized by progressive internal carotid artery stenosis and collateral vessel formation,prompts cerebral perfusion complications and is stratified into idiopathic and Moyamoya syndrome subtypes.A multifa-ceted approach toward MMD management addresses cerebral infarctions through revascularization surgery and adjunctive medical therapy,while also navigating risks such as intracranial hemorrhage and cerebral infarction resulting from arte-rial stenosis and fragile collateral vessels.Addressing antithrombotic management reveals a potential role for treatments like antiplatelet agents and anticoagulants,despite the ambiguous contribution of thrombosis to MMD-related infarctions and the critical balance between preventing ischemic events and averting hemo-rrhagic complications.Transcranial doppler has proven useful in thromboembolic detection,despite persisting challenges concerning the efficacy and safety of an-tithrombotic treatments.Furthermore,antihypertensive interventions aim to ma-nage blood pressure meticulously,especially during intracerebral hemorrhage,with recommendations and protocols varying based on the patient’s hypertension status.Additionally,lipid-lowering therapeutic strategies,particularly employing statins,are appraised for their possible beneficial role in MMD management,even as comprehensive data from disease-specific clinical trials remains elusive.Com-prehensive guidelines and protocols to navigate the multifaceted therapeutic ave-nues for MMD,while maintaining a delicate balance between efficacy and safety,warrant further meticulous research and development.This protocol manuscript seeks to elucidate the various aspects and challenges imbued in managing and navigating through the complex landscape of MMD treatment.

Outcome of COVID-19 infection in patients on antihypertensives:A cross-sectional study

BACKGROUND Patients with coronavirus disease 2019(COVID-19)infection frequently have hypertension as a co-morbidity,which is linked to adverse outcomes.Antihypertensives may affect the outcome of COVID-19 infection.AIM To assess the effects of antihypertensive agents on the outcomes of COVID-19 infection.METHODS A total of 260 patients were included,and their demographic data and clinical profile were documented.The patients were categorized into nonhypertensive,angiotensin-converting enzyme inhibitor/angiotensin receptor blocker(ACEI/ARB),calcium channel blocker(CCB),a combination of ACEI/ARB and CCB,and beta-blocker groups.Biochemical,hematological,and inflammatory markers were measured.The severity of infection,intensive care unit(ICU)intervention,and outcome were recorded.RESULTS The mean age of patients was approximately 60-years-old in all groups,except the nonhypertensive group.Men were predominant in all groups.Fever was the most common presenting symptom.Acute respiratory distress syndrome was the most common complication,and was mostly found in the CCB group.Critical cases,ICU intervention,and mortality were also higher in the CCB group.Multivariable logistic regression analysis revealed that age,duration of antihypertensive therapy,erythrocyte sedimentation rate,high-sensitivity C-reactive protein,and interleukin 6 were significantly associated with mortality.The duration of antihypertensive therapy exhibited a sensitivity of 70.8%and specificity of 55.7%,with a cut-off value of 4.5 years and an area under the curve of 0.670(0.574-0.767;95%confidence interval)for COVID-19 outcome.CONCLUSION The type of antihypertensive medication has no impact on the clinical sequence or mortality of patients with COVID-19 infection.However,the duration of antihypertensive therapy is associated with poor outcomes.

Epigallocatechin-3-gallate exerts antihypertensive effects and improves endothelial function in spontaneously hypertensive rats

Objective:To investigate the effect of epigallocatechin-3-gallate(EGCG)on endothelial dysfunction in spontaneously hypertensive rats(SHR).Methods:Wistar-Kyoto(WKY)rats and SHR were divided into four groups;WKY control,SHR control and SHR treated with EGCG(50 mg/kg/day)or losartan(10 mg/kg/day).The treatment was given daily for 4 weeks by oral gavage and the blood pressure was monitored by tail-cuff method every 3 days.Acetylcholineinduced endothelium-dependent relaxations were assessed in isolated phenylephrine-precontracted aortic rings at the end of treatment.The vascular levels of reactive oxygen species,nitric oxide,tetrahydrobiopterin,and cyclic guanosine monophosphate were also measured.Moreover,the expression of angiotensinⅡtype 1(AT_(1))receptor protein was determined.Results:The systolic blood pressure was significantly decreased in SHR treated with EGCG.The impaired endothelium-dependent relaxation was significantly improved in aortic ring isolated from the EGCG-treated SHR group.EGCG also significantly increased the levels of nitric oxide,tetrahydrobiopterin,and cyclic guanosine monophosphate,while decreasing the level of reactive oxygen species and the protein expression of AT_(1)receptor in SHR.Conclusions:EGCG attenuates endothelial dysfunction in SHR by decreasing oxidative stress and increasing vascular nitric oxide bioavailability,which may be modulated partly by inhibition of vascular AT_(1)receptors.An increase in endothelium-dependent relaxation may contribute to a decrease in blood pressure in hypertensive animals.

Synthesis of 2-Substituted Benzimidazol-N-biphenyl Acid and Crystal Structure of 4'-[(2-n-Propyl-1H-benzimidazol-1-yl)methyl] Biphenyl-2-carboxylate Acid

Nine analogues of telmisartan, 2-substituted benzimidazol-N-biphenyl acid, were designed and synthesized, from substituted benzimidazoles reacted with methyl 4'-(bromomethyl)- -biphenyl-2-carboxylate, then hydrolysis with KOH in MeOH and H2O. Their structures were confirmed by IR, 'H NMR, MS spectroscopy and elemental analysis. The crystal structure of 4'-[(2-n-propyl-1H-benzimidazol-lyl) methyl] biphenyl-2-carboxylic acid was determined by single crystal X-ray diffraction.

Association between serum homocysteine and arterial stiffness：role of anti-hypertensive drugs

To the Editor I read the article of Zhang, et al. with great interest. They investigated the association of homocysteine with arterial stiffness in Chinese community-based elderly persons. The carotid-femoral pulse wave velocity （PWV） was significantly higher in the high homocyteine group than in the normal one, however, there was no differences in carotid-radial PWV between the high homocyteine group and the normal one. Homocysteine levels were strongly associated with the carotidfemoral PWV even after adjustment for classical risk factors of cardiovascular disease. I congratulate the authors for this important study. However, I want to make minor criticism for this study from the methodological aspect.

Antihypertensive drugs and glucose metabolism

Hypertension plays a major role in the development and progression of micro-and macrovascular disease.Moreover,increased blood pressure often coexists with additional cardiovascular risk factors such as insulin resistance.As a result the need for a comprehensive management of hypertensive patients is critical.However,the various antihypertensive drug categories have different effects on glucose metabolism.Indeed,angiotensin receptor blockers as well as angiotensin converting enzyme inhibitors have been associated with beneficial effects on glucose homeostasis.Calcium channel blockers(CCBs)have an overall neutral effect on glucose metabolism.However,some members of the CCBs class such as azelnidipine and manidipine have been shown to have advantageous effects on glucose homeostasis.On the other hand,diuretics andβ-blockers have an overall disadvantageous effect on glucose metabolism.Of note,carvedilol as well as nebivolol seem to differentiate themselves from the rest of theβ-blockers class,being more attractive options regarding their effect on glucose homeostasis.The adverse effects of some blood pressure lowering drugs on glucose metabolism may,to an extent,compromise their cardiovascular protective role.As a result the effects on glucose homeostasis of the various blood pressure lowering drugs should be taken into account when selecting an antihypertensive treatment,especially in patients which are at high risk for developing diabetes.

A simple and efficient synthesis of the valsartan

Valsartan 1, one of the most important agents used in antihypertensive therapy today, was synthesized starting from L-valin methyl ester hydrochloride 2 through four steps in an overall yield of 60%. The key step involves the palladium-catalyzed Suzuki coupling. This method overcomes many of the drawbacks associated with the previously reported syntheses and is more suitable for industrial production.

Plants Used as Antihypertensive

Hypertension is a critical health problem and worse other cardiovascular diseases.It is mainly of two types:Primary or essential hypertension and Secondary hypertension.Hypertension is the primary possibility feature for coronary heart disease,stroke and renal vascular disease.Herbal medicines have been used for millions of years for the management and treatment of hypertension with minimum side effects.Over aim to write this review is to collect information on the anti-hypertensive effects of natural herbs in animal studies and human involvement as well as to recapitulate the underlying mechanisms,from the bottom of cell culture and ex-vivo tissue data.According to WHO,natural herbs/shrubs are widely used in increasing order to treat almost all the ailments of the human body.Plants are the regular industrial units for the invention of chemical constituents,they used as immunity booster to enhance the natural capacity of the body to fight against different health prob-lems as well as herbal medicines and food products also.Eighty percent population of the world(around 5.6 billion people)consume medicines from natural plants for major health concerns.This review provides a bird’s eye analysis primarily on the traditional utilization,phytochemical constituents and pharmacological values of medicinal herbs used to normalize hypertension i.e.Hibiscus sabdariffa,Allium sativum,Andrographis paniculata,Apium graveolens,Bidenspilosa,Camel-lia sinensis,Coptis chinensis,Coriandrum sativum,Crataegus spp.,Crocus sativus,Cymbopogon citrates,Nigella sativa,Panax ginseng,Salviaemiltiorrhizae,Zingiber officinale,Tribulus terrestris,Rauwolfiaserpentina,Terminalia arjuna etc.

Non-interventional management of resistant hypertension

Hypertension is one of the most popular fields of re-search in modern medicine due to its high prevalence and its major impact on cardiovascular risk and con-sequently on global health. Indeed, about one third of individuals worldwide has hypertension and is under increased long-term risk of myocardial infarction, stroke or cardiovascular death. On the other hand, resistant hypertension, the "uncontrollable" part of arterial hy-pertension despite appropriate therapy, comprises a much greater menace since long-standing, high levels of blood pressure along with concomitant debilitating entities such as chronic kidney disease and diabetes mellitus create a prominent high cardiovascular risk milieu. However, despite the alarming consequences, resistant hypertension and its effective management still have not received proper scientific attention. As-pects like the exact prevalence and prognosis are yet tobe clarified. In an effort to manage patients with resis-tant hypertension appropriately, clinical doctors are still racking their brains in order to find the best therapeutic algorithm and surmount the substantial difficulties in controlling this clinical entity. This review aims to shed light on the effective management of resistant hyper-tension and provide practical recommendations for cli-nicians dealing with such patients.

Antihypertensive Properties on Spontaneously Hypertensive Rats of Peptide Hydrolysates from Silkworm Pupae Protein

Peptide hydrolysates of silkworm pupae protein with molecular weight of less than 5000 Da were prepared by ultrafiltration. The extracted peptide hydrolysates of silkworm pupae protein had inhibitory action on angiotensin-I-converting enzyme activity in vitro. The hydrolysates were orally administered to spontaneously hypertensive rats (SHR) in one period and long-term (four weeks). The results showed that the systolic blood pressure (SBP) of the treatment groups decreased in a dose-related manner. After one oral administration of silkworm protein hydrolysates with doses of 60, 20 and 5 mg/kg, the SBP of SHR decreased by 21.5, 13.8, and 9.0 mmHg in 1.5 h. After four weeks of the treatment in 80 mg/kg, the SBP decreased by 25 mmHg, with the antihypertensive activity close to 4 mg/kg of captopril;the SBP of the 40 mg/kg dose group also decreased by 17.5 mmHg. The peptide hydrolysate did not affect the SBP in normal, non-hypertensive rats in one period and long-term treatments. The acute toxicity research showed that the peptide hydrolysates were safe and without side effects. This research would be helpful in exploring the silkworm protein peptides as functional components for the antihypertension treatment.

Effects of Magnetic Needle Acupuncture on Blood Pressure and Plasma ET-1 Level in the Patient of Hypertension

Endothelin-1 (ET-1) is ever known as a bio-peptidewith the strongest vasoconstrictive action and withwide biological effects.

Effect of morin, a flavonoid against DOCA-salt hypertensive rats:a dose dependent study

Objective:To determine the protective effect of morin, a flavonoid against deoxycorticosterone acetate(DOCA)-salt induced hypertension in male Wistar rats.Methods:Hypertension was induced in uninephrectomized rats by weekly twice subcutaneous injection of DOCA(25 mg/kg bw) and 1% NaCl in the drinking water for six consecutive weeks. Effect of morin against DOCA-salt induced hypertension was evaluated by measuring blood pressure and performing biochemical estimations and histopathological examination of renal tissues.Results:DOCA-salt hypertensive rats showed considerably increased systolic and diastolic blood pressure,serum hepatic marker enzyme activities such as aspartate aminotransferase(AST), alanine aminotransferase(ALT), alkaline phosphatase(ALP) and gamma-glutamyl transpeptidase(GGT)and renal function markers(urea, uric acid and creatinine) in plasma. Oral administration of morin(25, 50 and 75 mg/kg bw) brought back all the above parameters to near normal level.Histopathology of kidney also confirmed the biochemical findings of this study. The effect at a dose of 50 mg/kg bw of morin was more pronounced than that of the other two doses(25 and 75 mg/kg bw).Conclusions:These findings indicate that morin exhibits strong antihypertensive effect against DOCA-salt induced hypertension.

Novel synthesis of 2-butyl-5-chloro-3H-imidazole-4-carbaldehyde:A key intermediate of Losartan

A novel method for synthesis of 2-butyl-5 -chloro-3H-imidazole-4-carbaldehyde 2, a key intermediate of Losartan was reported. The compound 2 was synthesized from starting material dimethyl malonate 6 and n-valeronitrile 8 by six steps with an overall yield of 40%. The key step including the reaction of compound 5 with POCl3/DMF followed by hydrolysis to give compound 2 with the yield of 68%.

Factors associated with intensification of antihypertensive drug therapy in patients with poorly controlled hypertension

Objective To assess antihypertensive management of older patients with poor blood pressure(BP)control.Methods Physicians,voluntary participating in the study,included six consecutive hypertensive patients during routine visits.Hypertension had to have been previously recognized and averaged office BP was>140 and/or>90 mmHg in spite of>6 weeks of antihypertensive therapy.The physicians completed a questionnaire on patients'history of cardiovascular(CV)risk factors,comorbidities,home BP monitoring,anthropometric data and the pharmacotherapy.Results Mean age of the 6462 patients was 61 years,7%were>80 years,51%were female.Mean士SD office BP values were 158士13/92土10 mmHg.The most commonly prescribed antihypertensive drugs were:diuretics(67%),ACE inhibitors(64%),calcium channel blockers(58%)and卩-blockers(54%),and their use increased with age.On monotherapy or dual therapy,43%of the patients and 40%had their latest treatment modification within six months.Home BP monitoring was a factor that accelerated the modification of the therapy.Older patients had to have less chance on faster modification of antihypertensive therapy in spite of presence of diabetes and higher systolic BP.Conclusions Our study suggests that a large number of outpatients with poor BP control receive suboptimal antihypertensive therapy,especially in primary care.In older patients,higher BP values in the office settings are more frequently accepted by physicians even in case of higher CV risk.Regular home BP monitoring hastens the decision to intensify of antihypertensive treatment.

Twenty-four-hour ambulatory blood pressure changes in older patients with essential hypertension receiving monotherapy or dual combination antihypertensive drug therapy

Objective To evaluate the differences in 24-hour ambulatory blood pressure (BP) in older patients with hypertension treated with the five major classes of antihypertensive drugs,as monotherapy or dual combination therapy,to improve daytime and nighttime BP control. Methods We enrolled 1920 Chinese community-dwelling outpatients aged ≥ 60 years and compared ambulatory BP values and ambulatory BP control (24-hour BP < 130/80 mmHg;daytime mean BP < 135/85 mmHg;and nighttime mean BP < 120/70 mmHg),as well as nighttime BP dip patterns for monotherapy and dual combination therapy groups. Results Patients’ mean age was 71 years,and 59.5% of patients were women. Calcium channel blockers (CCBs) constituted the most common (60.3% of patients) monotherapy,and renin–angiotensin system (RAS) blockers combined with CCBs was the most common (56.5% of patients) dual combination therapy. Monotherapy with beta-blockers (BB) provided the best daytime BP control. The probabilities of having a nighttime dip pattern and nighttime BP control were higher in patients receiving diuretics compared with CCBs (OR = 0.52,P = 0.05 and OR = 0.41,P = 0.007,respectively). Patients receiving RAS/diuretic combination therapy had a higher probability of having controlled nighttime BP compared with those receiving RAS/CCB (OR = 0.45,P = 0.004). Compared with RAS/diuretic therapy,BB/CCB therapy had a higher probability of achieving daytime BP control (OR = 1.27,P = 0.45). Conclusions Antihypertensive monotherapy and dual combination drug therapy provided different ambulatory BP control and nighttime BP dip patterns. BB-based regimens provided lower daytime BP,whereas diuretic-based therapies provided lower nighttime BP,compared with other antihypertensive regimens.

Production of antihypertensive and antidiabetic peptide fractions from quinoa(Chenopodium quinoa Willd.)by electrodialysis with ultrafi ltration membranes

Processing bioactive peptides from natural sources using electrodialysis with ultrafiltration membranes(EDUF)have gained attention since it can fractionate in terms of their charge and molecular weight.Quinoa is a pseudo-cereal highlighted by its high protein content,amino acid profile and adapting growing conditions.The present work aimed at the production of quinoa peptides through fractionation using EDUF and to test the fractions according to antihypertensive and antidiabetic activity.Experimental data showed the production of peptides ranging between 0.4 and 1.5 k Da.Cationic(CQPF)(3.01%),anionic(AQPF)(1.18%)and the electrically neutral fraction quinoa protein hydrolysate(QPH)-EDUF(~95%)were obtained.In-vitro studies showed the highest glucose uptake modulation in L6 cell skeletal myoblasts in presence of QPH-EDUF and AQPF(17%and 11%)indicating potential antidiabetic activity.The antihypertensive effect studied in-vivo in spontaneously hypertensive rats(SHR),showed a decrease in systolic blood pressure in presence of the fractionated peptides,being 100 mg/kg a dose comparable to Captopril(positive control).These results contribute to the current knowledge of bioactive peptides from quinoa by reporting the relevance of EDUF as tool to produce selected peptide fractions.Nevertheless,further characterization is needed towards peptide sequencing,their respective role in the metabolism and scaling-up production using EDUF.

Process optimization,texture and microstructure of novel kelp tofu

Laminaria japonica Aresch as an edible and medicine dual-purpose marine algae,has been gradually accepted by people.Tofu was Chinese traditional food,combining kelp function ingredients with tofu has practical value.The extraction-optimization methodology and the sequences of kelp antihypertensive peptide(KAP)were investigated.The sensory,whiteness,water retention ability(WRA)and microstructure of KAP tofu were evaluated.The scanning electron microscope(SEM)results showed KAP addition(20%)significantly improved the tofu texture,with a denser network composed of relatively even pores.Compared with gypsum tofu and glucose-δ-interior fat(GDL)tofu,KAP tofu had significantly higher WRA(94.49±0.49)%and sensory evaluation score value(92.54±0.52),and a significantly lower IC_(50) value at(2.06±0.04)mg/mL(P<0.05).The maximum IC_(50) value(4.14 mg/mL)of kelp enzymatic hydrolysate was observed at enzyme(at an alkaline protease:trypsin ratio of 2:1)concentration 1.5%,temperature 55℃ and time 2 h.The sequences of 8 identified peptides were Lys-Tyr,Phe-Tyr,Gly-Lys-Tyr,Ala-Lys-Tyr,Ser-Lys-Thr-Tyr,Lys-Lys-Phe-Tyr,Lys-Phe-Lys-Tyr and Ala-Lys-Tyr-Ser-Tyr with IC_(50) values of 5.24,4.83,7.94,7.52,20.63,15.33,10.73 and 2.42μmol/L,respectively.These results indicated the potential use of KAP tofu as a valuable resource for development of functional foods.

Deprescribing antihypertensive treatment in nursing home patients and the effect on blood pressure

Background It is debatable whether treating multimorbid nursing home patients with antihypertensive drugs produces beneficial effects. Most cardiovascular guidelines promote treatment; few have advice on how to deprescribe when treatment may no longer be necessary. We investigated the effect of medication review on antihypertensive drug use and the association between cognition, blood pressure, and prescribing. Methods From August 2014 to December 2015, 765 patients from 72 units （clusters） in 32 Norwegian nursing homes were included in a 4-month, multicentre, cluster-randomized, controlled trial, with 9-month follow-up. Patients ≥ 65 years old with antihypertensive treatment （n = 295, 39%） were randomized to systematic medication review where the physician received support from peers （collegial mentoring） or were given care as usual （control condition）. Outcome measures were the number of antihypertensive drugs, systolic blood pressure, and pulse. We used hospitalizations and deaths as criteria to assess harm. Results At baseline, each patient used 9.2 ± 3.5 regular drugs, and 1.6 ± 0.7 antihypertensives. Mean blood pressure was 128/71 mmHg and 9% had a systolic pressure ≥ 160 mmHg. Between baseline and month four, antihypertensives were deprescribed to a significantly higher extent in the intervention group （n = 43, 32%） compared to control （n = 11, 10%）; Incidence Rate Ratio = 0.8, 95% CI = 0.7？0.9. In the intervention group, there was an immediate increase in systolic blood pressure when antihypertensives were reduced, from baseline 128 ± 19.5 mmHg to 143 ± 25.5 mmHg at month four. However, at month nine, the blood pressure had reverted to baseline values （mean 134 mmHg）. Deprescription did not affect pulse and systolic pressure. The number of hospitalizations was higher in control patients at month four （P = 0.031） and nine （P = 0.041）. Conclusion A systematic medication review supported by collegial mentoring significantly decreased the use of antihypertensive drugs in nursing home patients without an effect on the systolic blood pressure over time.

Angiotensin I converting enzyme(ACE)inhibitory activity and antihypertensive effects of rice peptides

In this paper,the antihypertension effect of rice peptide(RP)was studied.With spontaneously hypertensive rats(SHR)and Wistar Kyoto(WKY)as the research objects,RP disposable gastric and long-term gastric irrigation experiments were carried out and systolic blood pressure(SBP)was measured.At the end of the long-term gastric irrigation experiment,the content of nitric oxide(NO),angiotensin-converting enzyme(ACE),angiotensin II(Ang II)and renin in the plasma and the activity of ACE were determined.The results showed that RP could reduce systolic pressure of SHR and had time-dose dependence while high-dose RP signifi cantly reduced systolic pressure by 24.6 and 17.2 mm Hg,respectively after a single and long-term gastric irrigation test.RP also could inhibit the activity of ACE and increase the release of NO.These results suggested that the decompression mechanism of RP is likely to be related to the regulation of the renin-angiotensin system(RAS)and NO.