Vasodilatory Properties Research Articles

Conventional and advanced extraction methods of some bioactive compounds with health benefits of food and plant waste: A comprehensive review

AbstractFood bioactive compounds have a beneficial biological effect on human health, fending off cancer, cardiovascular disease, metabolic syndrome, and neurodegenerative disease, among other noncommunicable diseases and neurodegenerative disorders. Secondary metabolites like polyphenols, glucosinolates, carotenoids, vitamins, terpenoids, saponins, and fibers have been linked to these health benefits due to their antioxidant, antiatherogenic, anti‐inflammatory, antimicrobial, cardioprotective, and vasodilator properties. This review comprehensively illustrates the extraction of bioactive compounds in food formulations along plant wastes and provides insight into the efficient delivery systems for health‐promoting compounds. There is an insight into how to choose which bioactive to use, how to extract them in a bioavailable state, and how to include and deliver them. Grapes, garlic, sweet potato leaves, cactus pears, beetroot, amaranth, Picea abies bark waste, olive leaves, and black plum are discussed comprehensively in terms of extraction and health benefits. The novel and emerging technologies are discussed in detail, and a comprehensive review and comparison with conventional methods are presented. The significant health benefits associated with bioactive compounds are also discussed.

Vasopressin versus epinephrine during neonatal cardiopulmonary resuscitation of asphyxiated post-transitional piglets

BackgroundEpinephrine is currently the only recommended cardio-resuscitative medication for use in neonatal cardiopulmonary resuscitation (CPR), as per the consensus of science and treatment recommendations. An alternative medication, vasopressin, might be beneficial in neonatal CPR due to its combined pulmonary vasodilation and systemic vasoconstriction properties. AimWe aimed to compare the time to return of spontaneous circulation (ROSC) with administration of vasopressin or epinephrine during CPR of asphyxiated post-transitional piglets. MethodsNewborn piglets (n = 8/group) were anesthetized, tracheotomized and intubated, instrumented, and exposed to 50 min normocapnic hypoxia followed by asphyxia and cardiac arrest. Piglets were randomly allocated to receive vasopressin (Vaso, 0.4 U/kg) or epinephrine (Epi, 0.02 mg/kg) during CPR. Piglets were resuscitated with chest compressions superimposed with sustained inflations, and were administered either Vaso or Epi intravenously every 3 min until ROSC (max. 3 doses). Hemodynamic and cardiac function parameters were collected. Main ResultsThe median (IQR) time to ROSC was 106 (93–140) s with Vaso and 128 (100–198) s with Epi (p = 0.28). The number of piglets that achieved ROSC was 8 (100%) with Vaso and 7 (88%) with Epi (p = 1.00). Vaso-treated piglets had a significantly longer post-resuscitation survival time (240 (240–240) min) than Epi-treated piglets (65 (30–240) min, p = 0.02). Vaso-treated piglets had significantly improved carotid blood flow immediately after ROSC (p < 0.05), had longer duration of post-resuscitation hypertension (p = 0.05), and had significantly improved heart rate, arterial pressure, and cerebral blood oxygen saturation 4 h after ROSC (p < 0.05). ConclusionsVasopressin improved post-resuscitation survival and hemodynamics, and might be an alternative cardio-resuscitative medication during neonatal CPR, but further studies are warranted.

Study of analgesic and myotropic spasmolytic activity of alkylcarb

The work is devoted to the search for new biologically active substances in a series of alkylamides of dihydroquinoline-3-carboxylic acid. Analgesic properties of 30 newly synthesized substances were studied, which made it possible to identify the leader compound (provisional name alkylcarb) and recommend its effectiveness for further research as an antispasmodic agent for pain relief. It has been established experimentally, that the substance alkylcarb exhibits concentration-dependent vasodilatory properties in vitro on segments of the thoracic aorta of rats. The data, obtained in the work, justify the prospect of using the leader substance as a new analgesic and antispasmodic drug. The research expands and deepens knowledge about the pharmacological properties of alkylamide derivatives of dihydroquinoline-3-carboxylic acid.&#x0D; The aim of the work was to conduct screening studies to establish the analgesic activity of a newly synthesized series of chemical compounds among alkylamides of dihydroquinoline-3-carboxylic acid and to study the myotropic spasmolytic activity of the leader substance.&#x0D; Materials and methods. Analgesic properties of alkylamides of dihydroquinoline-3-carboxylic acid were studied on outbred white mice in the "acetic acid convulsions" test. During the experiment, the animals were treated in accordance with the International Principles of the European Convention for the Protection of Vertebrate Animals Used for Experiments and Other Scientific Purposes (Strasbourg, March 18, 1986). The studied substances were administered intragastrically to experimental animals at a dose of 10 mg/kg in the form of a finely dispersed aqueous suspension, stabilized with Tween-80. Voltaren at a dose of 8 mg/kg, recommended for preclinical studies, and analgin at a dose of 50 mg/kg were chosen as reference drugs.&#x0D; The studies of the contractile activity of smooth muscle vessels were carried out on segments of the thoracic aorta of rats of both sexes weighing 180-200 g. The studies of dilator reactions were carried out against the background of preliminary contraction with phenylephrine at a concentration of 10-6 mol/l. The antispasmodic efficiency of the new compound was determined in comparison with the classic antispasmodic drotaverine.&#x0D; The statistical processing of the results was carried out using the package of statistical analysis of electronic spreadsheets Exel, with the help of the program "Statgraphics Plus v. 3.0.” and the standard package of statistical programs "Statistica, V. 6.0". We used the Student's test, a non-parametric analog of univariate variance analysis - the Kruskal-Wallis test, and the Mann-Whitney test. Differences were considered statistically significant at p&lt;0.05.&#x0D; Results. The study of the analgesic activity of substances АO1-АO30 in the "acetic acid convulsion" test in mice showed that a compound АO26 (provisional name alkylcarb) has the most pronounced analgesic activity when administered intragastrically. In the "acetic acid convulsion" test, alkylcarb (10 mg/kg, per os) probably reduces the number of convulsions, caused by acetic acid. The level of activity of this compound is comparable to the activity of diclofenac (8 mg/kg, per os) and exceeds analgin (50 mg/kg, per os). The substance alkylcarb relieved vasospasm at the level of the comparison drug drotaverine in in vitro experiments on a model of an isolated fragment of the thoracic aorta of rats against the background of previous constriction with phenylephrine.&#x0D; Conclusion. Today, the search for new highly effective non-opioid analgesics is an urgent problem of modern pharmacology, since painkillers used in clinical practice do not meet the requirements of efficiency and safety. In this regard, in recent years, scientists of the National Pharmaceutical University have been intensively searching for new, highly effective substances with antinociceptive, anti-inflammatory and antipyretic effects among alkylamides of dihydroquinoline-3-carboxylic acid.

The free hydralazine anti-hypertensive drug and new salts with improved solubility

Although long used as an antihypertensive drug because of its vasodilator properties, Hydralazine (HDZ) has received renewed attention in the last few years due to its secondary therapeutic effects, which has led to its repurposing for its antioxidative, anti-apoptotic, and anti-inflammatory abilities, especially in cardiovascular and renal diseases. Given the worldwide prevalence of these diseases and that only the hydrochloride salt form of this drug has been reported and commercialized until now, in this paper we describe the synthesis, crystalline structure and physicochemical properties of the free hydralazine and its two new salts, a bromide (HDZ-Br) and a nitrate (HDZ-NO3), aiming to provide new candidates of HDZ solid forms that can be potentially used as an alternative to the pattern antihypertensive treatment, with better properties than the commercial one and can also be used in new applications addressed to this drug. Herein we investigated the three new multicomponent solid forms using single crystal X-ray diffraction (SCXRD), X-ray powder diffraction (XRPD), Differential Scanning Calorimetry (DSC), Thermogravimetric analysis (TGA), Infrared/Raman spectroscopies, and relative solubility studies. Interestingly, all structures showed the formation of HDZ columns intercalated with ions columns as well as a strong tendency to develop π···π stacking interactions among HDZ molecules which can be useful for future design of new potential multicomponent forms of HDZ. The new reported salts show a relative solubility higher than the commercially hydralazine hydrochloride form, suggesting that they can be potentially useful in new pharmaceutical formulations.

High-definition Cathodal Direct Current Stimulation for Treatment of Acute Ischemic Stroke

Cathodal transcranial direct current stimulation (C-tDCS) provides neuroprotection in preclinical models of acute ischemic stroke (AIS) by inhibiting peri-infarct excitotoxic effects and enhancing collateral perfusion due to its vasodilatory properties. To report the first-in-human pilot study using individualized high-definition (HD) C-tDCS as a treatment of AIS. This randomized clinical trial was sham controlled with 3 + 3 dose escalation design, and was conducted at a single center from October 2018 to July 2021. Eligible participants were treated for AIS within 24 hours from onset, had imaging evidence of cortical ischemia with salvageable penumbra, and were ineligible for reperfusion therapies. HD C-tDCS electrode montage was selected for each patient to deliver the electric current to the ischemic region only. Patients were followed for 90 days. Primary outcomes were feasibility, assessed as time from randomization to study stimulation initiation; tolerability, assessed by rate of patients completing the full study stimulation period; and safety, assessed by rates of symptomatic intracranial hemorrhage at 24 hours. The efficacy imaging biomarkers of neuroprotection and collateral enhancement were explored. A total of 10 patients with AIS were enrolled, 7 were randomized to active treatment and 3 to sham. Patient age was mean (SD) 75 (10) years old, 6 (60%) were female, and National Institutes of Health Stroke Scale score was mean (SD) 8 (7). Two doses of HD C-tDCS (1 milliamp [mA] for 20 minutes and 2 mA for 20 minutes) were studied. The speed of HD C-tDCS implementation was a median (IQR) 12.5 minutes (9-15 minutes) in the last 4 patients. Patients tolerated the HD C-tDCS with no permanent stimulation cessation. The hypoperfused region was reduced by a median (IQR) 100% (46% to 100%) in the active group vs increased by 325% (112% to 412%) in sham. Change in quantitative relative cerebral blood volume early poststimulation was a median (IQR) 64% (40% to 110%) in active vs -4% (-7% to 1%) sham patients and followed a dose-response pattern. Penumbral salvage in the active C-tDCS group was median (IQR) 66% (29% to 80.5%) vs 0% (IQR 0% to 0%) in sham. In this randomized, first-in-human clinical trial, HD C-tDCS was started efficiently and well tolerated in emergency settings, with signals of beneficial effect upon penumbral salvage. These results support advancing HD C-tDCS to larger trials. ClinicalTrials.gov Identifier: NCT03574038.

A negative trial for vasoactive intestinal peptide in COVID-19-associated acute hypoxaemic respiratory failure

A negative trial for vasoactive intestinal peptide in COVID-19-associated acute hypoxaemic respiratory failure

COMPARATIVE EFFECT OF ATENOLOL AND NEBIVOLOL ON REVERSE REMODELING OF INTRAMURAL CORONARY ARTERIOLES IN THE SPONTANEOUSLY HYPERTENSIVE RAT MODEL

Objective: Arterial hypertension is an established major risk factor for ischemic heart disease. Functional and structural abnormalities at the level of the microcirculation may play a crucial role in coronary microvascular dysfunction. Indeed, coronary flow reserve is often reduced at angiography in hypertensive patients independently on the presence of left ventricular hypertrophy (Mancini M. et al. Microcirculation 2017). The aim of this study was to assess the effect of the beta-blocker Atenolol and the selective third-generation beta1-adrenergic antagonist Nebivolol on markers of remodeling and endothelial dysfunction in coronary microvascular. Nebivolol has been demonstrated to possess direct vasodilator and antioxidant properties which may improve endothelial dysfunction and reduce smooth muscle cell proliferation. Design and method: For this purpose, we used three groups of SHR rats: Hypertensive untreated group (SHR); SHR plus Atenolol 50 mg/kg/day by oral gavaging for 8 weeks (SHR + ATE); SHR plus Nebivolol 20 mg/kg/day by oral gavaging for 8 weeks (SHR + NEB). Protein expression levels of vasoactive factors, oxidative stress and remodeling markers in coronary microcirculation were determined by immunohistochemical analysis of Endothelin-1 (ET-1), inducible nitric oxide synthase (iNOS) and transforming growth factor-beta1 (TGF-beta1). Results: No differences were observed in structural parameters of mesenteric arteries among groups. SHR + NEB showed a significant reduction in ET-1, iNOS, and TGF-beta1 staining in coronary small arteries comparing to SHR and SHR + ATE. Conclusions: In comparison to atenolol, nebivolol may provide additional benefit beyond blood pressure reduction and beta-receptor blockade since show greater activity in the modulation of protein involved in vasodilation and oxidative stress protection.

(090) Hydrogen Sulfide Therapy Stimulates Cellular Antioxidant Defense and Reverses Erectile Dysfunction in Western Diet-fed Mice

Abstract Introduction Hydrogen sulfide (H2S) is an endogenously produced gaseous cellular signaling molecule with vasodilatory, anti-inflammatory, and antioxidant-like properties. H2S is thought to protect against oxidative stress through activation of transcription factor(s) that transcribe genes involved cellular detoxification and antioxidant defense. We have previously used a Western diet (WD) high in fat and sugar to induce erectile dysfunction (ED) in rodents, in which excessive penile reactive oxygen species (ROS) have been implicated in ED pathogenesis. We have recently observed a reduction in protein content and activity of cystathionine γ-lyase, a major enzymatic source of H2S, in the corpus cavernosum of mice fed the WD for 12 weeks. Objective The objective of this study was to determine if chronic consumption of an orally active, slow releasing H2S prodrug (SG1002) can restore erectile function and alleviate WD-induced penile redox burden. Methods Young male C57Bl/6J mice (n = 120) were fed a control diet (CD) or WD ad libitum for 18 weeks. For the final six weeks of the dietary intervention, half of the mice were switched to an equivalent diet containing SG1002 at a concentration designed to deliver approximately 20 mg/kg/day. Following the intervention, erectile function was assessed by measuring intracavernosal pressure (ICP) and mean arterial pressure (MAP) during cavernous nerve stimulation (1, 2, 4 volts). In separate mice, in vivo ROS production was measured in the penis utilizing a microdialysis approach. Microdialysis probes were inserted into the penis of anesthetized mice and perfused with saline containing 100 μM Amplex Ultrared, 1 U/ml horseradish peroxidase, and 10 U/ml superoxide dismutase. ROS convert the reagents to a fluorescent byproduct resorufin, which was measured in the outflowing dialysate. In separate mice, naïve corpus cavernosum tissue was harvested for quantitative expression of 18 genes related to cellular antioxidant defense by qRT-PCR. Significant differences between groups were determined by two-way ANOVA with Tukey’s multiple comparisons post-hoc analysis, with an alpha level of 0.05. Results Erectile function was significantly impaired in the untreated WD-fed mice (CD: 64.8±8.4 vs. WD: 27.1±2.3; cumulative ICP area/MAP; p&amp;lt;0.01), while SG1002 induced a 74% functional restoration in WD mice (WD+SG1002: 51.0±2.8; p&amp;lt;0.05 vs. WD). Penile production of the ROS hydrogen peroxide and superoxide were elevated in the WD mice (CD: 0.71±0.07 vs. WD: 1.09 ±0.15; p&amp;lt;0.01), which were normalized by SG1002 treatment (WD+SG1002: 0.83±0.07; p&amp;lt;0.01 vs. WD). SG1002 had a positive stimulatory effect (p&amp;lt;0.05) on expression of ten of the antioxidant genes, including catalase, glutamate-cysteine ligase (gclc), glutathione peroxidase 1, glutathione peroxidase 4, peroxiredoxin 3, peroxiredoxin 5, thioredoxin reductase 1, heme oxygenase 1, sirtuin 1, and sirtuin 3. Conclusions H2S therapy with chronic SG1002 administration provides protection to the corpus cavernosum against an excessive ROS burden induced by the high-fat/high-sugar environment of the Western diet, likely through augmentation of the cellular antioxidant defense system. H2S therapy may be a promising strategy for treatment of early stage, obesity-associated erectile dysfunction. Disclosure No

Небіволол – бета-адреноблокатор з вазодилатаційними властивостями: досягнення і перспективи застосування

Огляд присвячений клінічному застосуванню β-адреноблокатора з вазодилатаційними властивостями – небівололу. Розглянуто основні фармакологічні властивості та характеристики препарату, його кардіоселективність та механізми вазодилатаційної дії. Показано особливості застосування небівололу в лікуванні есенціальної артеріальної гіпертензії, ішемічної хвороби серця та серцевої недостатності. Препарат не має діабетогенної дії при тривалому застосуванні, сприятливо впливає на показники ліпідного та вуглеводного обмінів. У хворих з ішемічною хворобою серця продемонстровано його антиангінальну й антиішемічну дію та зниження частоти рецидивів після виконання операцій на коронарних артеріях. Препарат добре толерується та має високу ефективність у зниженні показників смертності в пацієнтів віком понад 70 років з хронічною серцевою недостатністю, незалежно від фракції викиду лівого шлуночка. У лікуванні ішемічної хвороби серця при цукровому діабеті 2-го типу перевагу надають β-адреноблокаторам з вазодилатаційними властивостями. При необструктивних ураженнях коронарних артерій з-поміж β-адреноблокаторів перевагу надають небівололу для лікування мікросудинної стенокардії. У пацієнтів з артеріальною гіпертензією небіволол, крім антигіпертензивного ефекту, має сприятливий вплив на функцію ендотелію, метаболічний профіль, центральну гемодинаміку, якість життя пацієнтів, а також кращий профіль побічних ефектів.

A Perfusion Index-Based Evaluation and Comparison of Peripheral Perfusion in Sevoflurane and Isoflurane Anaesthesia: A Prospective Randomised Controlled Trial.

Perfusion index has shown to be helpful in the operative and critical care settings to monitor peripheral tissue perfusion. Randomised controlled trials quantifying different agents' vasodilatory properties using perfusion index has been limited. Therefore, we undertook this study to compare the vasodilatory effects of isoflurane and sevoflurane using perfusion index. This is a pre-specified sub-analysis of a prospective randomised controlled trial on the effects of inhalational agents at equipotent concentration. We randomly allocated patients scheduled for lumbar spine surgery to either isoflurane or sevoflurane groups. We recorded values of perfusion index at age-corrected 1 Minimum Alveolar Concentration (MAC) concentration at baseline, pre- and post-application of a noxious stimulus. The primary outcome of interest was the measure of vasomotor tone with perfusion index, and the secondary outcomes which were analysed were mean arterial pressure and heart rate. At age-corrected 1.0 MAC, there was no significant difference in the pre-stimulus haemodynamic variables and perfusion index between both groups. During the post-stimulus period, there was a significant increase in heart rate in the isoflurane group compared to the sevoflurane group, with no significant difference in the mean arterial pressure values between both groups. Though the perfusion index decreased during the post-stimulus period in both groups, there was no statistically significant difference between the 2 groups (P = .526, repeated-measures analysis of variance). In a steady state of age-corrected 1.0 MAC, isoflurane and sevoflurane had a similar perfusion index before and after a standardised nociceptive stimulus, which suggests that both of these agents have similar effect on peripheral perfusion and vasomotor tone.

Computational Insights into the Mechanism of Nitric Oxide Generation from S-Nitrosoglutathione Catalyzed by a Copper Metal-Organic Framework.

The controlled generation of nitric oxide (NO) from endogenous sources, such as S-nitrosoglutathione (GSNO), has significant implications for biomedical implants due to the vasodilatory and other beneficial properties of NO. The water-stable metal-organic framework (MOF) Cu-1,3,5-tris[1H-1,2,3-triazol-5-yl]benzene has been shown to catalyze the production of NO and glutathione disulfide (GSSG) from GSNO in aqueous solution as well as in blood. Previous experimental work provided kinetic data for the catalysis of the 2GSNO → 2NO + GSSG reaction, leading to various proposed mechanisms. Herein, this catalytic process is examined using density functional theory. Minimal functional models of the Cu-MOF cluster and glutathione moieties are established, and three distinct catalytic mechanisms are explored. The most thermodynamically favorable mechanism studied is consistent with prior experimental findings. This mechanism involves coordination of GSNO to copper via sulfur rather than nitrogen and requires a reductive elimination that produces a Cu(I) intermediate, implicating a redox-active copper site. The experimentally observed inhibition of reactivity at high pH values is explained in terms of deprotonation of a triazole linker, which decreases the structural stability of the Cu(I) intermediate. These fundamental mechanistic insights may be generally applicable to other MOF catalysts for NO generation.

11,12-EET suppressed LPS induced TF expression and thrombus formation by accelerating mRNA degradation rate via strengthening PI3K-Akt signaling pathway and inhibiting p38-TTP pathway

Epoxyeicosatrienoic acids (EETs), which are synthesized from arachidonic acid by cytochrome P450 epoxygenases, function primarily as autocrine and paracrine effectors in the cardiovascular system. So far, most research has focused on the vasodilatory, anti-inflammatory, anti-apoptotic and mitogenic properties of EETs in the systemic circulation. However, whether EETs could suppress tissue factor (TF) expression and prevent thrombus formation remains unknown. Here we utilized in vivo and in vitro models to investigate the effects and underlying mechanisms of exogenously EETs on LPS induced TF expression and inferior vein cava ligation induced thrombosis. We observed that the thrombus formation rate and the size of the thrombus were greatly reduced in 11,12-EET treated mice，accompanied by decreased TF and inflammatory cytokines expression. Further in vitro studies showed that by enhancing p38 MAPK activation and subsequent tristetraprolin (TTP) phosphorylation, LPS strengthened the stability of TF mRNA and induced increased TF expression. However, by strengthening PI3K-dependent Akt phosphorylation, which acted as a negative regulator of p38-TTP signaling pathway，11,12-EET reduced LPS-induced TF expression in monocytes. In addition, 11,12-EET inhibited LPS-induced NF-κB nuclear translocation by activating the PI3K/Akt pathway. Further study indicated that the inhibitory effect of 11,12-EET on TF expression was mediated by antagonizing LPS-induced activation of thromboxane prostanoid receptor. In conclusion, our study demonstrated that 11,12-EET prevented thrombosis by reducing TF expression and targeting the CYP2J2 epoxygenase pathway may represent a novel approach to mitigate thrombosis related diseases.

Aspirin-Dipyridamole in Fluctuating Small Vessel Disease Ischemic Strokes (P7-5.013)

<h3>Objective:</h3> Short-term inpatient use of aspirin-dipyridamole (Aggrenox) in small vessel disease (SVD) ischemic strokes (IS) may reduce neurologic fluctuations, leading to better functional outcomes. This single-center retrospective case-control study aims to compare outcomes in patients diagnosed with SVD IS who received Aggrenox versus standard antiplatelet therapy. <h3>Background:</h3> Aggrenox is a fixed-dose combination of aspirin, an antiplatelet, and extended-release dipyridamole, which acts both to impair platelet function and cause vasodilation. Previous studies showed Aggrenox to be safe and effective for secondary stroke prevention. We suspect that early use of Aggrenox could be effective for stroke prevention and functional outcomes due to its vasodilatory properties. <h3>Design/Methods:</h3> A retrospective analysis of patients diagnosed with SVD IS between January 2016–December 2020 was completed. We plan to enroll patients admitted through September 2022. Patients with age ≥18, who received a minimum of four doses of Aggrenox during hospitalization, will be matched with control patients who did not receive Aggrenox. Study end points include discharge NIHSS compared hospital day 1 and discharge mRS compared to admission. REDCap is being used for data collection and generation of descriptive statistics. <h3>Results:</h3> Thus far, 49 patients have qualified for inclusion into the Aggrenox cohort, with data collection still in progress. Subject pool has mean age 55; 49% male; 82% African American; 49% diabetic; 37% received tPA; mean length of time from admission to administration of Aggrenox of 26 hours; mean duration of Aggrenox 4 days; mean NIHSS on admission 5.7; mean NIHSS on discharge 5.1; mean mRS at admission 0.6; mean mRS at discharge 2.7; 41% of patients discharged home, 57% to inpatient rehabilitation, and 2% to a skilled nursing facility. <h3>Conclusions:</h3> Data in the Aggrenox population shows a trend toward improvement in NIHSS throughout hospitalization. Once control group data is collected, comparative statistics will be used to analyze outcomes between the two groups. <b>Disclosure:</b> Dr. Moran has nothing to disclose. Dr. March has nothing to disclose. Dr. Nearing has nothing to disclose.

Current achievements and prospects for the use of nebivolol in the treatment of patients with cardiovascular diseases

A literature review deals with the clinical use of nebivol as a beta-blocker (BB) with vasodilating properties. The principal pharmacological properties and characteristics of the drug, its cardioselectivity and mechanisms of vasodilation are presented. The special place of nebivolol in the treatment of essential arterial hypertension (AH), coronary heart disease (CHD) and heart failure (HF) is outlined. The drug does not possess a diabetogenic activity with a long-term use, and impacts favourably on the parameters of lipid and carbohydrate metabolism. In CHD patients, nebivolol demonstrates the anti-anginal and anti-ischemic activities, and reduces the frequency of angina recurrence after coronary artery interventions. The drug is well tolerated and characterized by a high effectiveness with respect to the reduction of mortality rates in patients with chronic HF over 70 years of age, regardless of the left ventricular ejection fraction. Vasodilating BB are preferred in the treatment of CHD patients with type 2 diabetes. In case of non-obstructive coronary lesions, nebivolol is chosen among existing BBs for the treatment of microvascular angina. The use of nebivolol in AH patients, in addition to the antihypertensive effect, is characterized by a favorable impact on the function of endothelium, the metabolic profile, central hemodynamics, health-related quality of life of patients, as well as more favorable profile of side effects.

Pinocembrin inhibits migration and invasion of nonsmall cell lung cancer cells by inhibiting STAT3 signaling

Background: In cancer treatment, targeting the activation of signal transducer and activator of transcription 3 (STAT3) is crucial as it promotes tumor progression and metastasis through the process of epithelial-mesenchymal transition (EMT). Pinocembrin, a dihydroxyflavanone found naturally in propolis and honey, is known for its antioxidant and vasodilating properties. The objective of this study is to explore the potential of pinocembrin in regulating the STAT3 signaling pathway to inhibit migration and invasion of nonsmall cell lung cancer (NSCLC) cells.&#x0D; Methods: Hematoxylin staining was used to determine the migration and invasion of A549 cells. The relative expression of EMT-related proteins and invasive proteins in A549 cells was determined by Western blot analysis. STAT3 activity was evaluated using a luciferase assay. Overexpression of STAT3 was utilized to assess the role of pinocembrin in regulating STAT3.&#x0D; Results: Pinocembrin treatment (50 μM) significantly reduced the number of migrating and invasive cells. Pinocembrin upregulated the protein level of E-cadherin and downregulated the protein levels of N-cadherin and vimentin. Additionally, pinocembrin blocked the phosphorylation and activation of STAT3. Overexpression of STAT3 reversed the inhibitory effects of pinocembrin on cell migration and invasion.&#x0D; Conclusion: Our study demonstrates that pinocembrin can inhibit the activation of STAT3, which is associated with EMT and thereby attenuate migration and invasion in NSCLC cells.

Three Generation β-Blockers for Atrial Fibrillation Treatment.

The efficiency of blood flowing from the heart depends on its electrical properties. Myocardial electrical activity is associated with generating cardiac action potentials in isolated myocardial cells and their coordinated propagation, which are mediated by gap junctions. Atrial fibrillation (AF) is a common cardiac arrhythmia which causes an aggressive disturbance in cardiac electromechanical function. Moreover, AF increases the risk of stroke and mortality and is a major cause of death. The mechanisms underlying AF involve electrophysiological changes in ion channel expression and function. β-blockers may be useful in patients with chronic AF or in preventing postoperative AF in subjects undergoing coronary artery bypass grafting (CABG) or other types of surgery. The reduction in heart rate induced by β1-adrenergic receptor antagonists may be associated with the beneficial effect of this drug class. Second generation beta-blockers may be considered superior to the first generation due to their selectivity to the β1 receptor as well as avoiding pulmonary or metabolic adverse effects. Third generation beta-blockers may be considered a great option for their vasodilation and antioxidant properties. There is also a new β-blocker, named landilol that also results on reduced risk of post operative AF without adverse effects and its use has been increasing in clinical trials.

Phytochemical Contents and Antioxidant potentials of Eggplants from Kano State, Nigeria: A Review

Fruits and vegetables are considered as good source of functional foods due to their health benefits and nutritional content. Dietary constituents of fruits and vegetable are commonly available and has significant application in management of chronic diseases such as; coronary heart disease, stroke, cancer and diabetes, many medicinal purposes, control of excess weight and obesity due to high fiber content present. Many phenolic compounds had been identified in garden eggplant such as; catechin, rutin, naringin, naringenin, syringic acid, chlorogenic acid, caffeic acid, p-coumaric acid, sinapic acid and anthocyanin. Health-conscious consumers generally focus on the antioxidant capacity, and the phenolic content, vitamins, carotenoids and phytochemicals. All varieties of garden egg vary in polyphenol endowed with antioxidant activity. Polyphenolic compounds and antioxidant activity in eggplants which depend on the cultivar, maturity stage and parts of the fruit. Growing conditions are also reported to significantly affect the phenolic contents. This review discussed the polyphenolic contents and antioxidant activities of different eggplant cultivars. Priority was given to green, white and dark-purple cultivars which are commonly grown in Nigeria. White and green eggplants possess higher phenolic contents when compared with dark purple eggplant which possesses higher antioxidant capacity. They contain about 92% water, 5% protein, copper (0.62mg/100g), magnesium (81.69mg/100g), potassium (87.22mg/100g), sodium (32.51mg/100g), irons (31.41mg/100g), zinc (1.41mg/100g), carbohydrate (7.2 g/100g), fibers (2.0g/100g), calcium (28 mg/100g), iron (1.5 mg/100g) and considerable amount of beta carotene (0.35 mg/100g), ascorbic acid (8 mg/100g), riboflavin (0.06 mg/100g) and thiamin (0.07 mg/100g). The species of African eggplant have nutritional and therapeutic values and can be used in the development of functional foods and these bioactive compounds are responsible for high functions of eggplants and provide antibacterial, anti-inflammatory, anti-allergic, hepatoprotective, antithrombotic, antiviral, anti-carcinogenic and vasodilatory properties in humans.

Effectiveness of beta-blockers in the therapy of arterial hypertension

Recently, the interest of the cardiology community has been focused on the results of the latest studies on the use of vasodilating β-blockers in patients with arterial hypertension. A review of these studies demonstrates a number of advantages over conventional cardioselective drugs (without vasodilator properties). The positive features of vasodilating β-adrenoblockers are proven metabolic neutrality, proportional reduction of central and peripheral blood pressure, minimal effect on bronchial patency, the absence of negative effect on erectile function, reduction in the frequency of cardiovascular complications in patients with arterial hypertension.

Endothelial KCa3.1 and KCa2.3 Mediate S1P (Sphingosine-1-Phosphate)-Dependent Vasodilation and Blood Pressure Homeostasis.

S1P (sphingosine-1-phosphate) has been reported to possess vasodilatory properties, but the underlying pathways are largely unknown. Isolated mouse mesenteric artery and endothelial cell models were used to determine S1P-induced vasodilation, intracellular calcium, membrane potentials, and calcium-activated potassium channels (KCa2.3 and KCa3.1 [endothelial small- and intermediate-conductance calcium-activated potassium channels]). Effect of deletion of endothelial S1PR1 (type 1 S1P receptor) on vasodilation and blood pressure was evaluated. Mesenteric arteries subjected to acute S1P stimulation displayed a dose-dependent vasodilation response, which was attenuated by blocking endothelial KCa2.3 or KCa3.1 channels. In cultured human umbilical vein endothelial cells, S1P stimulated immediate membrane potential hyperpolarization following activation of KCa2.3/KCa3.1 with elevated cytosolic Ca2+. Further, chronic S1P stimulation enhanced expression of KCa2.3 and KCa3.1 in human umbilical vein endothelial cells in dose- and time-dependent manners, which was abolished by disrupting either S1PR1-Ca2+ signaling or downstream Ca2+-activated calcineurin/NFAT (nuclear factor of activated T-cells) signaling. By combination of bioinformatics-based binding site prediction and chromatin immunoprecipitation assay, we revealed in human umbilical vein endothelial cells that chronic activation of S1P/S1PR1 promoted NFATc2 nuclear translocation and binding to promoter regions of KCa2.3 and KCa3.1 genes thus to upregulate transcription of these channels. Deletion of endothelial S1PR1 reduced expression of KCa2.3 and KCa3.1 in mesenteric arteries and exacerbated hypertension in mice with angiotensin II infusion. This study provides evidence for the mechanistic role of KCa2.3/KCa3.1-activated endothelium-dependent hyperpolarization in vasodilation and blood pressure homeostasis in response to S1P. This mechanistic demonstration would facilitate the development of new therapies for cardiovascular diseases associated with hypertension.

The Role of Rehabilitation in Arterial Function Properties of Convalescent COVID-19 Patients.

Coronavirus disease (COVID-19) is a respiratory disease, although arterial function involvement has been documented. We assess the impact of a post-acute COVID-19 rehabilitation program on endothelium-dependent vasodilation and arterial wall properties. We enrolled 60 convalescent patients from COVID-19 and one-month post-acute disease, who were randomized at a 1:1 ratio in a 3-month cardiopulmonary rehabilitation program (study group) or not (control group). Endothelium-dependent vasodilation was evaluated by flow-mediated dilation (FMD), and arterial wall properties were evaluated by carotid-femoral pulse wave velocity (cf-PWV) and augmentation index (AIx) at 1 month and at 4 months post-acute disease. FMD was significantly improved in both the study (6.2 ± 1.8% vs. 8.6 ± 2.4%, p < 0.001) and control groups (5.9 ± 2.2% vs. 6.6 ± 1.8%, p = 0.009), but the improvement was significantly higher in the study group (rehabilitation) (p < 0.001). PWV was improved in the study group (8.2 ± 1.3 m/s vs. 6.6 ± 1.0 m/s, p < 0.001) but not in the control group (8.9 ± 1.8 m/s vs. 8.8 ± 1.9 m/s, p = 0.74). Similarly, AIx was improved in the study group (25.9 ± 9.8% vs. 21.1 ± 9.3%, p < 0.001) but not in the control group (27.6 ± 9.2% vs. 26.2 ± 9.8 m/s, p = 0.15). Convalescent COVID-19 subjects of the study group (rehabilitation) with increased serum levels of circulating IL-6 had a greater reduction in FMD. Conclusively, a 3-month cardiopulmonary post-acute COVID-19 rehabilitation program improves recovery of endothelium-dependent vasodilation and arteriosclerosis.