Relaxation Of Blood Vessels Research Articles

Prunus yedoensis Bark Downregulates the Expression of Cell Adhesion Molecules in Human Endothelial Cell Lines and Relaxes Blood Vessels in Rat Aortic Rings.

The incidence of cardiovascular diseases, such as high blood pressure, is increasing worldwide, owing to population aging and irregular lifestyle habits. Previous studies have reported the vasorelaxant effects of Prunus yedoensis bark methanol extract. However, various solvent extracts of P. yedoensis bark and their vascular relaxation mechanisms have not been sufficiently studied. We prepared extracts of P. yedoensis bark using various solvents (water, 30% ethanol, and 70% ethanol). P. yedoensis bark 30% ethanol extract (PYB-30E) decreased the expression of vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), and E-selectin in human umbilical vein endothelial cells (HUVECs) activated with 200 ng/mL TNF-α. Additionally, PYB-30E showed vasodilatory effects on isolated rat aortic rings. This was confirmed to be the result of the activation of the NO/cGMP pathway, regulation of non-selective calcium-activated K+ channels, and calcium channel blockade. Additionally, PYB-30E significantly reduced systolic and diastolic blood pressure in spontaneously hypertensive rats (SHR). Taken together, our results indicated that PYB-30E is a candidate functional material with preventive and therapeutic effects against hypertension.

Nfluence of extracellular acidosis on the functional contribution of KATP and TASK-1 potassium channels to the regulation of vascular tone in early postnatal ontogenesis

The activity of many proteins and, as a result, of the mechanisms of vascular tone regulation depends on pH. A decrease of pH (uncompensated acidosis), usually causes relaxation of blood vessels, which has been studied in sufficient detail for an adult, matured organism. However, the effect of acidosis on the mechanisms of vascular tone regulation in the early postnatal period remains almost completely unexplored. The aim of this work was to study the effect of extracellular metabolic acidosis on the functional contribution of KATP and TASK-1 potassium channels to the regulation of vascular tone in early postnatal period. We modeled extracellular metabolic acidosis (pH 6.8, equimolar replacement of NaHCO3 with NaCl in solution) and studied isometric contractile responses of the saphenous artery in rats aged 3–4 months and rat pups aged 12–15 days. Arterial contraction to the α1-adrenergic agonist methoxamine at pH 6.8 was reduced compared to normal pH 7.4 in both 3–4-month-old and 12–15-day-old rats. The KATP channel blocker glibenclamide did not change the arterial responses to methoxamine, neither at pH 7.4 nor at pH 6.8 in any of the age groups. The TASK-1 channel blocker AVE1231 did not alter arterial contractile responses at any pH in 3–4-month-old rats. However, in 12–15-day-old rat pups, the increase in contractile responses to methoxamine under the influence of AVE1231 was less at pH 6.8 than at pH 7.4. Thus, the results of this work demonstrate that acidosis reduces the contractile activity of the arteries of 3–4-month-old animals and animals during early postnatal ontogenesis, while in the latter, the anticontractile role of TASK-1 channels decreases, and KATP channels do not affect the regulation of vascular tone, either under normal, or at acidic pH in any of the age groups.

Binder-free and efficient voltammetric sensor based on Zn-Ca2CuO3 nanoparticles for simultaneous determination of amlodipine, acetaminophen, and ascorbic acid in hypertension patients.

Amlodipine (AM) is a long active calcium channel blocker used to relax blood vessels by preventing calcium ion transport into the vascular walls and its supporting molecules acetaminophen (AP) and ascorbic acid (AA) are recommended for hypertension control and prevention. Considering their therapeutic importance and potential side effects due to over dosage, we have fabricated a sensor for individual and simultaneous determination of AA, AP, and AM in pharmaceuticals and human urine using novel Zn-doped Ca2CuO3 nanoparticles modified glassy carbon electrode (GCE). Optimally doped Ca2CuO3 (2.5 wt% Zn at Cu site) enhanced the detection of target molecules over much wider concentration ranges of 50 to 3130 µM for AA, 0.25 to 417 µM for AP, and 0.8 to 354 µM for AM with the corresponding lowest detection limits of 14 µM, 0.05 µM, and 0.07 µM, respectively. Furthermore, the Zn-Ca2CuO3/GCE exhibited excellent selectivity and high sensitivity even in the presence of several potential interfering agents. The usefulness of the developed electrode was tested using an amlodipine besylate tablet and urine samples of seven hypertension patients under medication. The results confirmed the presence of a significant amount of AP and AM in six patients' urine samples indicating that the personalized medication is essential and the quantum of medication need to be fixed by knowing the excess medicines excreted through urine. Thus, the Zn-Ca2CuO3/GCE with a high recovery percentage and good sensitivity shall be useful in the pharmaceutical and biomedical sectors.

The interplay of hydrogen sulfide and microRNAs in cardiovascular diseases: insights and future perspectives.

Hydrogen sulfide (H2S) is recognized as the third gasotransmitter, after nitric oxide (NO) and carbon monoxide (CO). It is known for its cardioprotective properties, including the relaxation of blood vessels, promotion of angiogenesis, regulation of myocardial cell apoptosis, inhibition of vascular smooth muscle cell proliferation, and reduction of inflammation. Additionally, abnormal H2S generation has been linked to the development of cardiovascular diseases (CVD), such as pulmonary hypertension, hypertension, atherosclerosis, vascular calcification, and myocardial injury. MicroRNAs (miRNAs) are non-coding, conserved, and versatile molecules that primarily influence gene expression by repressing translation and have emerged as biomarkers for CVD diagnosis. Studies have demonstrated that H2S can ameliorate cardiac dysfunction by regulating specific miRNAs, and certain miRNAs can also regulate H2S synthesis. The crosstalk between miRNAs and H2S offers a novel perspective for investigating the pathophysiology, prevention, and treatment of CVD. The present analysis outlines the interactions between H2S and miRNAs and their influence on CVD, providing insights into their future potential and advancement.

Role of Cinnamomum verum leaves in the management of Vascular dementia: A comprehensive overview

Spices are utilized for both culinary and medicinal purposes and have been for a very long time originating from Sri Lanka and southern India, Cinnamomum verum may also be found in other Asian, Caribbean, Australian, and African countries. The principal compounds contained are Cinnamaldehyde and Eugenol, both of which have unique medicinal qualities in the leaves of Cinnamomum verum. Cinnamonaldehyde (CA), a bioactive phytochemical offer therapeutic advantages against the beginning of cardiovascular illnesses. Eugenol is an organic compound found in the leaves of Cinnamomum verum. Eugenol has antihypercholesterolemic and antiatherogenic effects. Eugenol's smooth muscle relaxant effect is due to its inhibition of receptor-operated and voltage-sensitive channels. Endothelial cells create nitric oxide (NO), which relaxes blood vessels. Eugenol has substantial anti-inflammatory properties. The antipyretic activity of eugenol is well recognized, since it reduces fever by reducing prostaglandin and sodium archidonate synthesis. Eugenol's hydrophobic nature allows it to pass the blood-brain barrier and enter the brain. Eugenol protects neuronal cells against the oxidative and excitotoxic effects of N-methyl-D-aspartate (NDMA). Eugenol has neuroprotective properties in hippocampal tissues due to its capacity to reduce brain-derived neurotrophic factor (BDNF) and postpone amyloid β -peptide (A- β) induced cell death via abnormal Ca2+ blocking. Anti-hypertensive property of Eugenol is known as it has the ability to activate TRPV channels and to relax endothelium-depleted arteries. Eugenol, which is found in Cinnamomum verum leaves, has been shown to be beneficial in the control of hypertension and so may be beneficial in the management of vascular dementia.

Red light mediates the exocytosis of vasodilatory vesicles from cultured endothelial cells: a cellular, and ex vivo murine model

We have previously established that 670 nm energy induces relaxation of blood vessels via an endothelium derived S-nitrosothiol (RSNO) suggested to be embedded in vesicles. Here, we confirm that red light facilitates the exocytosis of this vasodilator from cultured endothelial cells and increases ex vivo blood vessel diameter. Ex vivo pressurized and pre-constricted facial arteries from C57Bl6/J mice relaxed 14.7% of maximum diameter when immersed in the medium removed from red-light exposed Bovine Aortic Endothelial Cells. In parallel experiments, 0.49 nM RSNO equivalent species was measured in the medium over the irradiated cells vs dark control. Electron microscopy of light exposed endothelium revealed significant increases in the size of the Multi Vesicular Body (MVB), a regulator of exosome trafficking, while RSNO accumulated in the MVBs as detected with immunogold labeling electron microscopy (1.8-fold of control). Moreover, red light enhanced the presence of F-actin related stress fibers (necessary for exocytosis), and the endothelial specific marker VE-cadherin levels suggesting an endothelial origin of the extracellular vesicles. Flow cytometry coupled with DAF staining, an indirect sensor of nitric oxide (NO), indicated significant amounts of NO within the extracellular vesicles (1.4-fold increase relative to dark control). Therefore, we further define the mechanism on the 670 nm light mediated traffic of endothelial vasodilatory vesicles and plan to leverage this insight into the delivery of red-light therapies.Graphical abstract

Mechanism of Action of Many Drugs Depend on Enzyme Inhibition

Enzyme inhibition is an important process in the mode of action of many drugs used in the treatment of various diseases. Antibiotics, anti-hypertensive agents, anti-hyperlipidaemic, anti-glaucoma, and anti-malarial drugs act on specific enzymes, leading to bacteriostatic or bactericidal effects, lower blood pressure, reduce cholesterol levels, and cause smooth muscle relaxation of blood vessels. Understanding the mode of action of these drugs and how they affect enzymes is crucial for the development of new drugs and the optimization of existing therapies. This article highlights some various drugs that act through enzyme inhibition and their mechanisms of action.

G6PD Deficiency: Exploring the Relationship with Different Medical Disorders

G6PD deficiency (G6PDD) is associated with oxidative stress resulting from an imbalance between reactive oxygen species (ROS) production and the body's ability to counteract. In this review, we explore the adverse effects of G6PDD on diverse physiological processes and disease outcomes. Past studies have demonstrated the association between G6PDD and various other diseases, indicating a link between G6PDD to heightened oxidative stress by accelerating virus replication, worsening infection severity, and weakening the body's defense mechanisms. Such stress is critical in the destruction of red blood cells (RBCs) during infections and has a detrimental impact on redox signaling, ultimately impacting cell health and promoting cancer development. Furthermore, it impairs endothelial function by lowering the nitric oxide (NO) level and increasing stress, resulting in detrimental cardiac consequences and reduced myocardial antioxidant capacity. Because ROS contributes to inflammation, this imbalance causes conditions such as early atherosclerosis. It also compromises the functionality of NO-regulated bronchodilators and conditions such as G6PDD exacerbate the risks of kidney damage. Elevated ROS levels can also induce harm in retinal tissues, blood vessels, brain cells, and Beta-cells, hence quickening the progression of diseases like Diabetic Retinopathy. Furthermore, oxidative stress plays a significant role in cerebral ischemic pathogenesis, contributing to neurodegenerative disorders. Additionally, decreased NADPH level is vital for NO synthesis as it can impact blood vessel relaxation and can potentially lead to ischaemic priapism. Investigating the association between G6PDD and other medical conditions is crucial as it helps to identify possible approaches to mitigate oxidative stress, thereby preventing associated complications and diseases, particularly in situations where current treatment options are insufficient.

Reduced Nitric Oxide Synthase Involvement in Aigamo Duck Basilar Arterial Relaxation.

The basilar arterial endothelium mediates blood vessel relaxation partly through the release of nitric oxide (NO). Apoptosis of cerebrovascular endothelial cells is linked to a high mortality rate in chickens infected with the highly pathogenic avian influenza virus, but interestingly, ducks exhibit a greater resistance to this virus. In this study, we examined the responsiveness of duck basilar arteries (BAs) to various vasoactive substances, including 5-hydroxytryptamine (5-HT), histamine (His), angiotensin (Ang) II, noradrenaline (NA), acetylcholine (ACh), and avian bradykinin ornithokinin (OK), aiming to characterize the receptor subtypes involved and the role of endothelial NO in vitro. Our findings suggest that arterial contraction is mediated with 5-HT1 and H1 receptors, while relaxation is induced with β3-adrenergic and M3 receptors. Additionally, OK elicited a biphasic response in duck BAs, and Ang II had no effect. Endothelial NO appears to be crucial in relaxation mediated with M3 and OK receptors but not β3-adrenergic receptors in the duck BA. The reduced endothelial NO involvement in the receptor-mediated relaxation response in duck BAs represents a clear difference from the corresponding response reported in chicken BAs. This physiological difference may explain the differences in lethality between ducks and chickens when vascular endothelial cells are infected with the virus.

Medicinal plant rosemary relaxes blood vessels by activating vascular smooth muscle KCNQ channels.

The evergreen plant rosemary (Salvia rosmarinus) has been employed medicinally for centuries as a memory aid, analgesic, spasmolytic, vasorelaxant and antihypertensive, with recent preclinical and clinical evidence rationalizing some applications. Voltage-gated potassium (Kv) channels in the KCNQ (Kv7) subfamily are highly influential in the nervous system, muscle and epithelia. KCNQ4 and KCNQ5 regulate vascular smooth muscle excitability and contractility and are implicated as antihypertensive drug targets. Here, we found that rosemary extract potentiates homomeric and heteromeric KCNQ4 and KCNQ5 activity, resulting in membrane hyperpolarization. Two rosemary diterpenes, carnosol and carnosic acid, underlie the effects and, like rosemary, are efficacious KCNQ-dependent vasorelaxants, quantified by myography in rat mesenteric arteries. Sex- and estrous cycle stage-dependence of the vasorelaxation matches sex- and estrous cycle stage-dependent KCNQ expression. The results uncover a molecular mechanism underlying rosemary vasorelaxant effects and identify new chemical spaces for KCNQ-dependent vasorelaxants.

The effect of temperature on vascular smooth muscle: cooling-induced vasodilation in deep arteries and veins.

Blood vessels in the cardiovascular system include arteries and veins, which are responsible for moving blood to and from tissues around the body. Our previous studies showed that cooling induces relaxation of arteries. The aim of this study is to investigate the effect of cooling on both arteries and veins pairs. Isometric tension was recorded in rat artery ring preparations (aorta, carotid, pulmonary arteries) and their vein pairs (vena cava, jugular, pulmonary veins) in organ baths during stepwise cooling from 37 to 4°C. Cooling responses were tested before and after the addition of various standard agents. The possibility of the presence of a cooling-relaxed substance and the influence of endothelium were also examined. Cooling-induced relaxation of both arteries and veins and the degree of relaxation were inversely proportional to the temperature. The cooling response was highest in arteries than their respective paired veins. The relaxation response was not endothelium dependent or affected with neurogenic mechanism (autonomic blockers or tetrodotoxin). Additionally, it was not changed by alterations of extra- or intra-cellular calcium transfer, and no relaxant substance was released from vascular smooth muscles during cooling. The study showed that cooling induces relaxation of both arteries and veins. Our results suggested that the effect of cooling could be through a thermal receptor in the vascular smooth muscle. Therefore, cold temperature can act as an agonist and increase in cooling temperature behaves as increase in concentration of the agonist. This study contributes to a better understanding of the mechanisms behind cooling-induced relaxation of blood vessels, which may have implications for the treatment of cardiovascular diseases.

Downregulation of connexin 43-based gap junctions underlies propofol-induced excessive relaxation in hypertensive vascular smooth muscle cells

BackgroundPostinduction hypotension caused by propofol remains a non-negligible problem for anesthesiologists, and is especially severe in chronic hypertensive patients with long-term vasoconstriction and decreased vascular elasticity. The functional change in gap junctions composed of Cx43 (Cx43-GJs) is reported as the biological basis of synchronized contraction or relaxation of blood vessels. Thus, we investigated the role of Cx43-GJs in propofol-induced dramatic blood pressure fluctuations in chronic hypertensive patients, and their internal mechanisms.MethodsHuman umbilical artery smooth muscle cells (HUASMCs) were pretreated with long-term angiotensin II (Ang II), with or without propofol, to simulate the contraction and relaxation of normal and hypertensive VSMCs during anesthesia induction. The levels of F-actin polymerization and MLC2 phosphorylation were used as indicators to observe the contraction and relaxation of HUASMCs. Different specific activators, inhibitors and siRNAs were used to explore the role of Cx43-GJs and Ca2+ as well as the RhoA/ LIMK2/cofilin and RhoA/MLCK signaling pathways in the contraction and relaxation of normal and hypertensive HUASMCs.ResultsBoth F-actin polymerization and MLC2 phosphorylation were significantly enhanced in Ang II-pretreated HUASMCs, along with higher expression of Cx43 protein and stronger function of Cx43-GJs than in normal HUASMCs. However, with propofol administration, similar to Gap26 and Cx43-siRNA, the function of Cx43-GJs in Ang II-pretreated HUASMCs was inhibited compared with that in normal HUASMCs, accompanied by a larger decrease in intracellular Ca2+ and the RhoA/LIMK2/cofilin and RhoA/MLCK signaling pathways. Eventually F-actin polymerization and MLC2 phosphorylation were more dramatically decreased. However, these effects could be reversed by RA with enhanced Cx43-GJ function.ConclusionLong-term exposure to Ang II significantly enhanced the expression of the Cx43 protein and function of Cx43-GJs in HUASMCs, resulting in the accumulation of intracellular Ca2+ and the activation of its downstream RhoA/LIMK2/cofilin and RhoA/MLCK signaling pathways, which maintained HUASMCs in a state of excessive-contraction. With inhibition of Cx43-GJs by propofol in Ang II-pretreated HUASMCs, intracellular Ca2+ and its downstream signaling pathways were dramatically inhibited, which ultimately excessively relaxed HUASMCs. This is the reason why the blood pressure fluctuation of patients with chronic hypertension was more severe after receiving propofol induction.9gEgDUsF4_-ddhb1iAhQGKVideo

The FAT1 Cadherin Drives Vascular Smooth Muscle Cell Migration.

Vascular smooth muscle cells (VSMCs) are normally quiescent and non-migratory, regulating the contraction and relaxation of blood vessels to control the vascular tone. In response to arterial injury, these cells become active; they proliferate, secrete matrix proteins, and migrate, and thereby contribute importantly to the progression of several cardiovascular diseases. VSMC migration specifically supports atherosclerosis, restenosis after catheter-based intervention, transplant vasculopathy, and vascular remodeling during the formation of aneurysms. The atypical cadherin FAT1 is expressed robustly in activated VSMCs and promotes their migration. A positive role of FAT1 in the migration of other cell types, including neurons, fibroblasts, podocytes, and astrocyte progenitors, has also been described. In cancer biology, however, the effect of FAT1 on migration depends on the cancer type or context, as FAT1 either suppresses or enhances cancer cell migration and invasion. With this review, we describe what is known about FAT1's effects on cell migration as well as the factors that influence FAT1-dependent migration. In VSMCs, these factors include angiotensin II, which activates FAT1 expression and cell migration, and proteins of the Atrophin family: Atrophin-1 and the short isoform of Atrophin-2, which promote VSMC migration, and the long isoform of Atrophin-2, which exerts negative effects on FAT1-dependent VSMC migration.

Review on the protective mechanism of astragaloside IV against cardiovascular diseases.

Cardiovascular disease is a global health problem. Astragaloside IV (AS-IV) is a saponin compound extracted from the roots of the Chinese herb Astragalus. Over the past few decades, AS-IV has been shown to possess various pharmacological properties. It can protect the myocardium through antioxidative stress, anti-inflammatory effects, regulation of calcium homeostasis, improvement of myocardial energy metabolism, anti-apoptosis, anti-cardiomyocyte hypertrophy, anti-myocardial fibrosis, regulation of myocardial autophagy, and improvement of myocardial microcirculation. AS-IV exerts protective effects on blood vessels. For example, it can protect vascular endothelial cells through antioxidative stress and anti-inflammatory pathways, relax blood vessels, stabilize atherosclerotic plaques, and inhibit the proliferation and migration of vascular smooth muscle cells. Thus, the bioavailability of AS-IV is low. Toxicology indicates that AS-IV is safe, but should be used cautiously in pregnant women. In this paper, we review the mechanisms of AS-IV prevention and treatment of cardiovascular diseases in recent years to provide a reference for future research and drug development.

Alpha 7-nicotinic cholinergic regulation of pericyte-containing retinal capillaries.

Local blood flow regulation relies mostly on the coordination between neurons and pericyte-containing capillaries. Pericyte relaxation and contraction are influenced by various vasoactive substances and regulated by neurotransmitters. α7 nicotinic acetylcholine receptors (α7-nAChRs), involved in the regulation of vascular function and inhibitory GABA systems, have neuroprotective effects against central nervous system diseases. Although α7-nAChRs are found throughout the retina, their contribution to the retinal capillary tone remains unknown. Here we investigate the neurovascular coupling mechanism underlying α7-nAChR-mediated retinal capillary tone regulation. Changes in capillary diameter and transverse diameter of pericytes during drug perfusion were observed using differential interference contrast microscopy (DIC) to elucidate signaling pathways underlying α7-nAChR-mediated regulation of capillary blood flow at the whole retinal level. Patch clamp technique was used to investigate α7-nAChRs-mediated regulation of the γ-aminobutyric acid (GABA) synaptic circuit. Immunofluorescence was used to explore the expression of α7-nAChRs and GABA receptors. Activating α7-nAChRs on the endothelial cell membrane caused perinuclear accumulation of eNOS. This resulted in dilated retinal capillaries and pericytes via the NOS/NO-cGMP signaling pathway. Neuronal α7-nAChRs activation relaxed retinal capillaries and pericytes via a neurovascular coupling mechanism. α7-nAChR increased the vesicular release of GABA, possibly promoting the release of NO by binding to GABAA receptors in retinal ganglionic cells (RGCs), and relaxation of blood vessels via eNOS-NO by binding to GABAB receptors on retinal capillary endothelial cells. α7-nAChR activation causes vasorelaxation of retinal capillaries.

Vasodilatory constituents of essential oil from Nardostachys jatamansi DC.: Virtual screening, experimental validation and the potential molecular mechanisms

Recent studies have demonstrated that the essential oil of Nardostachys jatamansi (EONJ) has potential health benefits, such as reducing blood pressure, protecting the heart, and relaxing blood vessels. However, the active constituents and the underlying molecular mechanisms are still unclear. In this study, we utilized GC–MS to identify the chemical constituents of EONJ and tested its vasodilatory effects on constricted isolated thoracic aorta rings from mice. We then combined network pharmacology with spectrum-effect relationship approaches to select potential marker ingredients and uncover the possible vascular protective mechanism of EONJ. Among the four main chemicals screened in this work, β-maaliene and patchouli alcohol exhibited varying levels of vasodilatory effects on isolated, constricted thoracic aortic rings. Bioinformatics and network pharmacology analyses revealed that EONJ's primary biological regulation targets were NOS3 and PTGS2. Moreover, EONJ may exert its vasodilatory effects by modulating lipid and atherosclerosis and the PI3K-AKT signaling pathways. This study provides the first report on the vasodilatory effects and possible molecular mechanisms of EONJ. The findings may serve as a reference for quality evaluation, identification of bioactive markers, and future applications of EONJ in the prevention and treatment of vascular and cardiac diseases.

Effects of the different Tai Chi exercise cycles on patients with essential hypertension: A systematic review and meta-analysis.

The main treatment for essential hypertension at this stage is pharmacotherapy. Long-term pharmacotherapy is costly with some side effects. Tai Chi, a bright star in traditional Chinese arts, relaxes both mind and body and has been shown to relax blood vessels and lower blood pressure. This study aimed to systematically review the therapeutic effectiveness of the Tai Chi exercise cycle on blood pressure and cardiovascular risk factors of patients with essential hypertension. Searching CNKI, VIP, CBM, PubMed, EBSCO, Embase, Cochrane Library, and Web of Science to collect randomized controlled trials about Tai Chi exercise in the treatment of patients with essential hypertension according to the inclusion and exclusion criteria. The search time ranged from the date of database construction to December 2022. The Cochrane risk-of-bias tool was used to evaluate the included trials. The meta-analysis was performed with RevMan5.3 and Stata12.0 software. According to the meta-analysis, compared with the controls, Tai Chi exercise with a cycle of more than 12 weeks may be better for the reduction of systolic blood pressure (SBP) [MD = -11.72, 95% CI (-15.52, -7.91)] and diastolic blood pressure (DBP) [MD = -4.68, 95% CI (-7.23, -2.12)], as well as increasing the content of nitric oxide (NO) [MD = 0.99, 95% CI (0.69, 1.28)]. The blood lipid metabolism ability may also be improved after more than 12 weeks of Tai Chi exercise, total cholesterol (TC) [SMD = -0.68, 95% CI (-0.89, -0.46), triglyceride (TG) [SMD = -0.84, 95% CI (-1.25, -0.43)], low-density lipoprotein cholesterol (LDL-C) [SMD = -1.58, 95% CI (-2.29, -0.86)]. However, the improvement of high-density lipoprotein cholesterol (HDL-C) [SMD = 0.54, 95% CI (0.28, 0.79)] was better with a less than 12 weeks exercise cycle. A subgroup analysis for exercise frequency and time showed that the exercise frequency should preferably be more than or equal to 5 times per week for patients with hypertension, and for patients with hypertension plus hyperlipidemia, the exercise frequency less than 5 times per week with exercise time less than 60 min each day may be more beneficial. The meta-analysis indicated that a more than 12 weeks Tai Chi exercise cycle with less than 60 min each time and more than 5 times per week may be more beneficial in blood pressure reduction, NO level increasing and blood lipid metabolism improving in the comparison with the other exercise cycles. For patients with hypertension plus hyperlipidemia, exercise frequency of less than 5 times per week may be better. [http://www.crd.york.ac.uk/prospero], identifier [CRD42022352035].

Diminazene aceturate uses different pathways to induce relaxation in healthy and atherogenic blood vessels

Diminazene aceturate (DIZE), a putative angiotensin-converting enzyme 2 (ACE2) activator, elicits relaxation in various animal models. This study aimed to determine the relaxing mechanisms in internal iliac arteries utilised by DIZE in healthy and atherogenic rabbit models. Studies were conducted on internal iliac artery rings retrieved from male New Zealand White rabbits fed a 4-week healthy control (n = 24) or atherogenic diet (n = 20). To investigate pathways utilised by DIZE to promote arterial relaxation, a DIZE dose response [10-9.0 M – 10-5.0 M] was performed on pre-contracted rings incubated with pharmaceuticals that target: components of the renin-angiotensin system; endothelial- and vascular smooth muscle-dependent mechanisms; protein kinases; and potassium channels. ACE2 expression was quantified by immunohistochemistry analysis following a 2 hr or 4 hr DIZE incubation. DIZE significantly enhanced vessel relaxation in atherogenic rings at doses [10-5.5 M] (p < 0.01) and [10-5.0 M] (p < 0.0001), when compared to healthy controls. Comprehensive results from functional isometric studies determined that DIZE causes relaxation via different mechanisms depending on pathology. For the first time, we report that in healthy blood vessels DIZE exerts its direct relaxing effect through ACE2/AT2R and NO/sGC pathways; however, in atherogenesis this switches to MasR, arachidonic acid pathway (i.e., COX1/2, EET and DHET), MCLP, Ca2+ activated voltage channels, AMPK and ERK1/2. Moreover, quantitative immunohistochemical analysis demonstrated that DIZE increases artery ACE2 expression in a time dependent manner. We provide a detailed investigation of DIZE’s mechanisms and demonstrate for the first time that in healthy and atherogenic arteries DIZE provides beneficial effects through directly inducing relaxation, albeit via different pathways.

GENE POLYMORPHISM AS A PREDICTOR DEVELOPMENT OF THE CHILDREN DISEASE

Neonates suffering from severe birth asphyxia may develop hypoxic ischemic encephalopathy and in some cases to permanent neurological damage. Around 20 – 50% of neonates with birth asphyxia who have hypoxic ischemic encephalopathy symptoms die in the neonatal period. Our study aims to clarify the role and impact of gene polymorphisms on the occurrence of hypoxic-ischemic encephalopathy. Hypoxic-ischaemic encephalopathy is a common cause of death and disability in newborns. It causes long-term or permanent damage, such as cerebral palsy, epilepsy, and certain forms of mental retardation. Autoregulation may be impaired during various neonatal disease and states including prematurity, hypoxic-ischemic encephalopathy, intraventricular haemorrhage, congenital cardiac disease, and infants requiring extracorporeal membrane oxygenation. As infants are especially sensitive to changes in cerebral blood flow, both hypoperfusion and hyperperfusion can cause significant neurologic injury. All of these conditions impair cerebral blood flow, leading to ischemia and hypoxia and trigger a cascade of deleterious biochemical events that seriously and permanently injure the brain. The nitric oxide produced by NOS3 plays a critical role in maintaining cerebral blood circulation and preventing neuronal injury. Mild exposure to ischemia activates enzyme NOS3 and produces small amounts of nitric oxide with subsequent relaxation of blood vessels and vasodilatation. Genetic factors could also affect the processes of autoregulation and destruction following hypoxic-ischemic injury. An underlying genetic predisposition that increases or decreases the degree of injury after a prenatal hypoxic ischemic event may affect the clinical course and prognosis. Except of therapeutic hypothermia, which currently is the only treatment available, a considerable number of newborns still have adverse outcomes. Therefore, there is a pressing need for novel better prognostic and diagnostic tools to improve outcome.

Pengaruh Pemberian Air Seduhan Serbuk Simplisia Seledri (Apium Graveolens) Terhadap Penurunan Tekanan Darah Pada Penderita Hipertensi.

Hypertension is a major risk factor for cardiovascular disease which is a major cause of death worldwide. The purpose of thisstudy was to determine the effect of water administration of celery powder (Apium graveolens) on blood pressure reductionin hypertensive patients. Celery (Apium graveolens) contains Apigenin which can prevent narrowing of the arteries(vasodilation) and Pthalides which can relax the artery muscles or relax blood vessels (vasorelaxation). This research usesfield observation method with a case study approach. Pre-treatment and post-treatment design. The results of the study of casestudies 1, 2, 3 and 4 showed an average result of a decrease in systolic pressure of 57.5 mmHg and diastolic of 25 mmHg.Study 5 as a control obtained results in lower blood pressure reduction. The conclusion of this study is the provision of watersteeping powder of celery simplicia influences in the form of decreased blood pressure and improved quality of life of patientswith hypertension.