scholarly journals 3-Hydroxyphenylacetic Acid: A Blood Pressure-Reducing Flavonoid Metabolite

Nutrients ◽  
2022 ◽  
Vol 14 (2) ◽  
pp. 328
Author(s):  
Patrícia Dias ◽  
Jana Pourová ◽  
Marie Vopršalová ◽  
Iveta Nejmanová ◽  
Přemysl Mladěnka
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Ex Vivo ◽  
Laboratory Animals ◽  
Spontaneously Hypertensive ◽  
Porcine Coronary Artery ◽  
Arterial Blood ◽  
Hydroxyphenylacetic Acid ◽  
Dose Dependent Decrease

Regular intake of polyphenol-rich food has been associated with a wide variety of beneficial health effects, including the prevention of cardiovascular diseases. However, the parent flavonoids have mostly low bioavailability and, hence, their metabolites have been hypothesized to be bioactive. One of these metabolites, 3-hydroxyphenylacetic acid (3-HPAA), formed by the gut microbiota, was previously reported to exert vasorelaxant effects ex vivo. The aim of this study was to shed more light on this effect in vivo, and to elucidate the mechanism of action. 3-HPAA gave rise to a dose-dependent decrease in arterial blood pressure when administered i.v. both as a bolus and infusion to spontaneously hypertensive rats. In contrast, no significant changes in heart rate were observed. In ex vivo experiments, where porcine hearts from a slaughterhouse were used to decrease the need for laboratory animals, 3-HPAA relaxed precontracted porcine coronary artery segments via a mechanism partially dependent on endothelium integrity. This relaxation was significantly impaired after endothelial nitric oxide synthase inhibition. In contrast, the blockade of SKCa or IKCa channels, or muscarinic receptors, did not affect 3-HPAA relaxation. Similarly, no effects of 3-HPAA on cyclooxygenase nor L-type calcium channels were observed. Thus, 3-HPAA decreases blood pressure in vivo via vessel relaxation, and this mechanism might be based on the release of nitric oxide by the endothelial layer.

ESR spectral transition by arteriovenous cycle in nitric oxide hemoglobin of cytokine-treated rats

1994 ◽  
Vol 266 (5) ◽  
pp. C1400-C1405 ◽  
Author(s):  
H. Kosaka ◽  
Y. Sawai ◽  
H. Sakaguchi ◽  
E. Kumura ◽  
N. Harada ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Hyperfine Structure ◽  
Ex Vivo ◽  
Interleukin 1 ◽  
Venous Blood ◽  
Esr Spectra ◽  
Arterial Blood ◽  
Spin Resonance ◽  
Necrosis Factor

Nitric oxide (NO) generation was induced in rats by Escherichia coli lipopolysaccharide (LPS) as detected by electron spin resonance (ESR) signals of NO hemoglobin (HbNO). However, there were inconsistencies in ESR spectral shape among them. We have therefore carried out a systematic study to clarify the in vivo spectral changes. First, the spectra of the alpha-NO heme species had the distinct three-line hyperfine structure in venous blood but not in arterial blood in all rats treated with tumor necrosis factor, interleukin-1, and/or LPS, and methemoglobin was not detected at the g = 6 (high-spin methemoglobin) region. Second, when the treated rats died, the three-line hyperfine structure was very distinct even in arterial blood. Third, even if HbNO was formed by injection of nitrite to rats, the three-line hyperfine structure of HbNO in venous blood was more marked than that in arterial blood, independent of the appearance of the methemoglobin signal. Fourth, an ex vivo study using whole blood demonstrated that the three-line hyperfine structure intensified lineally when O2 saturation of hemoglobin decreased but disappeared on reoxygenation of hemoglobin. These results directly demonstrate in vivo quaternary structural transition of the hemoglobin tetramer from the high-affinity state in the arterial cycle to the low-affinity state in the venous cycle. The transition makes the diverse ESR spectra of HbNO in vivo.

Abstract 167: A Cell-Autonomous Role for Endothelial GTP Cyclohydrolase 1 and Tetrahydrobiopterin in Blood Pressure Regulation

2014 ◽  
Vol 34 (suppl_1) ◽  
Author(s):  
Surawee Chuaiphichai ◽  
Eileen McNeill ◽  
Gillian Douglas ◽  
Mark J Crabtree ◽  
Jennifer K Bendall ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Endothelial Cell ◽  
De Novo ◽  
Soluble Guanylate Cyclase ◽  
Ex Vivo ◽  
Mesenteric Arteries ◽  
Gtp Cyclohydrolase ◽  
Enos Uncoupling

Tetrahydrobiopterin (BH4) is an essential cofactor for endothelial nitric oxide synthase (eNOS) function and nitric oxide (NO) generation. Augmentation of BH4 levels can prevent eNOS uncoupling and improve endothelial dysfunction in vascular disease states. However, the physiological requirement for de-novo endothelial cell BH4 biosynthesis in eNOS function remains unclear. We generated a novel mouse model with endothelial cell-specific deletion of GCH1, encoding GTP cyclohydrolase 1, an essential enzyme for BH4 biosynthesis, to test the cell-autonomous requirement for endothelial BH4 biosynthesis in vivo. Mice with a floxed GCH1 allele ( GCH1 fl/fl ) were crossed with Tie2cre mice to delete GCH1 in endothelial cells. GCH1 fl/fl Tie2cre mice demonstrated virtually absent NO bioactivity and significantly greater O 2 • - production. GCH1 fl/fl Tie2cre aortas and mesenteric arteries had enhanced vasoconstriction to phenylephrine and impaired endothelium-dependent vasodilatations to acetylcholine and SLIGRL. Endothelium-dependent vasodilatations in GCH1 fl/fl Tie2cre aortas were in part mediated by NOS-derived hydrogen peroxide (H 2 O 2 ), which mediated vasodilatation through soluble guanylate cyclase. Ex vivo supplementation of aortic rings with the BH4 analogue sepiapterin restored normal endothelial function and abolished eNOS-derived H 2 O 2 production in GCH1 fl/fl Tie2cre aortas. GCH1 fl/fl Tie2cre mice had higher systemic blood pressure than wild-type littermates, which was normalised by NOS inhibitor, L-NAME. Taken together, these studies reveal an endothelial cell-autonomous requirement for GCH1 and BH4 in regulation of vascular tone and blood pressure, and identify endothelial cell BH4 as a pivotal regulator of NO vs. H 2 O 2 as alternative eNOS-derived endothelial derived relaxing factors.

Antihypertensive effect of mechanism-based inhibition of renal arachidonic acid ω-hydroxylase activity

2002 ◽  
Vol 283 (3) ◽  
pp. R710-R720 ◽  
Author(s):  
Fengyun Xu ◽  
Wesley O. Straub ◽  
Winnie Pak ◽  
Ping Su ◽  
Kristopher G. Maier ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Spontaneously Hypertensive Rat ◽  
Spontaneously Hypertensive ◽  
Arterial Blood ◽  
Vasoconstrictor Response ◽  
Potent Vasoconstrictor ◽  
Acetylenic Fatty Acid ◽  
Regulation Of Blood Pressure

The cytochrome P-450 eicosanoid 20-hydroxyeicosatetraenoic acid (20-HETE) is a potent vasoconstrictor that is implicated in the regulation of blood pressure. The identification of selective inhibitors of renal 20-HETE formation for use in vivo would facilitate studies to determine the systemic effects of this eicosanoid. We characterized the acetylenic fatty acid sodium 10-undecynyl sulfate (10-SUYS) as a potent and selective mechanism-based inhibitor of renal 20-HETE formation. A single dose of 10-SUYS caused an acute reduction in mean arterial blood pressure in 8-wk-old spontaneously hypertensive rats. The decrease in mean arterial pressure was maximal 6 h after 10-SUYS treatment (17.9 ± 3.2 mmHg; P < 0.05), and blood pressure returned to baseline levels within 24 h after treatment. Treatment with 10-SUYS was associated with a decrease in urinary 20-HETE formation in vivo and attenuation of the vasoconstrictor response of renal interlobar arteries to ANG II in vitro. These results provide further evidence that 20-HETE plays an important role in the regulation of blood pressure in the spontaneously hypertensive rat.

Abstract 15: Novel Functions of Small GTPase Rap1 in Regulating Endothelial Homeostasis: Control of Nitric Oxide Release, Vascular Function and Blood Pressure

2014 ◽  
Vol 34 (suppl_1) ◽  
Author(s):  
Sribalaji Lakshmikanthan ◽  
Xiaodong Zheng ◽  
Yoshinori Nishijima ◽  
Jeannette Vasquez-Vivar ◽  
David X Zhang ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Shear Flow ◽  
Knockout Mice ◽  
Ex Vivo ◽  
Left Ventricular ◽  
Small Gtpase ◽  
No Production ◽  
Endothelial Homeostasis

Endothelial dysfunction, resulting from decreased nitric oxide (NO) bioavailability is a pathology linked to endothelial vasomotor dysfunction and hypertension, inflammation and atherosclerosis, perturbed endothelial barrier and progression of diabetes. In blood vessels, NO is produced by the endothelial NO synthase (eNOS), the activity of which is regulated by Ca2+/calmodulin, binding of regulatory cofactors, and posttranslational modifications, including phosphorylation events on Ser1177, which stimulate NO production. Rap1 is a ubiquitously expressed small GTPase implicated in promoting vascular barrier. We have shown that endothelial cell (EC)-specific Rap1 deletion leads to defective angiogenesis in vivo due to faulty VEGFR2 activation and signaling. Importantly, EC-specific Rap1 knockout mice developed hypertension and pathological left ventricular hypertrophy. The objective of the study was to determine the role of small G protein Rap1 in regulating endothelial NO production and endothelial-dependent vasorelaxation in vivo and ex vivo. Using ex vivo myography and tamoxifen-inducible, endothelial-specific Rap1-knockout mice (Cadh5-CreERT2+/0;Rap1f/f), we demonstrate that Rap1 deficiency completely abrogates NO-dependent vasodilation and attenuates NO production. Mechanistically, we show that Rap1 is rapidly activated in response to receptor agonists that activate eNOS via Ca2+/calmodulin- dependent pathway and in response to shear flow, which modules eNOS activity by its phosphorylation. Rap1 deletion in human ECs, in vitro, leads to deficient NO release in response to both these stimuli, and interferes with PI3K/Akt pathway and eNOS Ser1177 phosphorylation. Further, we demonstrate Rap1 is required for transducing signals from the endothelial mechanosensing complex comprising PECAM-1, VE-cadherin and VEGFR2 in response to shear flow, leading to ligand-independent VEGFR2 activation and signaling to stimulate NO production. We conclude that Rap1 in endothelium is critically required for endothelial homeostasis and NO production, thereby affecting vascular tone and regulation of blood pressure. Furthermore, this study establishes Rap1 as a novel regulator of mechanotransduction in response to shear flow.

scholarly journals Partial Agonist Activity of Neonicotinoids on Rat Nicotinic Receptors: Consequences over Epinephrine Secretion and In Vivo Blood Pressure

2021 ◽  
Vol 22 (10) ◽  
pp. 5106
Author(s):  
Joohee Park ◽  
Antoine Taly ◽  
Jennifer Bourreau ◽  
Frédéric De Nardi ◽  
Claire Legendre ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Nervous System ◽  
Nicotinic Acetylcholine Receptors ◽  
Ex Vivo ◽  
Partial Agonist ◽  
Simultaneous Exposure ◽  
Vegetative Nervous System ◽  
Arterial Blood

Neonicotinoid insecticides are nicotine-derived molecules which exert acute neurotoxic effects over the insect central nervous system by activating nicotinic acetylcholine receptors (nAChRs). However, these receptors are also present in the mammalian central and peripheral nervous system, where the effects of neonicotinoids are faintly known. In mammals, cholinergic synapses are crucial for the control of vascular tone, blood pressure and skeletal muscle contraction. We therefore hypothesized that neonicotinoids could affect cholinergic networks in mammals and sought to highlight functional consequences of acute intoxication in rats with sub-lethal concentrations of the highly used acetamiprid (ACE) and clothianidin (CLO). In this view, we characterized their electrophysiological effects on rat α3β4 nAChRs, knowing that it is predominantly expressed in ganglia of the vegetative nervous system and the adrenal medulla, which initiates catecholamine secretion. Both molecules exhibited a weak agonist effect on α3β4 receptors. Accordingly, their influence on epinephrine secretion from rat adrenal glands was also weak at 100 M, but it was stronger at 500 M. Challenging ACE or CLO together with nicotine (NIC) ended up with paradoxical effects on secretion. In addition, we measured the rat arterial blood pressure (ABP) in vivo by arterial catheterization. As expected, NIC induced a significant increase in ABP. ACE and CLO did not affect the ABP in the same conditions. However, simultaneous exposure of rats to both NIC and ACE/CLO promoted an increase of ABP and induced a biphasic response. Modeling the interaction of ACE or CLO on α3β4 nAChR is consistent with a binding site located in the agonist pocket of the receptor. We present a transversal experimental approach of mammal intoxication with neonicotinoids at different scales, including in vitro, ex vivo, in vivo and in silico. It paves the way of the acute and chronic toxicity for this class of insecticides on mammalian organisms

Regulation of in vivo whole blood aggregation in rats by calcitonin gene related peptide

1998 ◽  
Vol 76 (7-8) ◽  
pp. 811-813 ◽  
Author(s):  
Brian P Booth ◽  
Ho-Leung Fung
Keyword(s):  
Blood Pressure ◽  
Whole Blood ◽  
Ex Vivo ◽  
Calcitonin Gene Related Peptide ◽  
Physiological Control ◽  
Duration Of Action ◽  
Related Peptide ◽  
Arterial Blood ◽  
Calcitonin Gene

The purpose of these experiments was to determine whether calcitonin gene related peptide (CGRP) mediates physiological control of platelet function in vivo. Rat blood pressure was continuously monitored via a femoral arterial cannula, and whole blood aggregation was assessed periodically ex vivo with an impedance aggregometer before and following a 1.4 nmol/kg bolus dose of CGRP8-37, a specific receptor antagonist of CGRP. Mean arterial blood pressure was not significantly affected by CGRP8-37 over a 30-min period (p > 0.05). However, whole blood aggregation increased by 38.4 ± 18.0% (p < 0.01) and 32.0 ± 11.2% (p < 0.05), at 5 and 15 min post CGRP8-37, respectively, when compared with control. Whole blood aggregation was not significantly different from control at 30 min (p > 0.05), suggesting a relatively short duration of action for in vivo CGRP8-37. These data suggest that CGRP contributes to the maintenance of hemostasis, and that this function may be more important than the better known vasodilatatory effects of this neuropeptide.Key words: hemostasis, calcitonin gene related peptide (CGRP), CGRP8-37, blood pressure, platelet aggregation.

Early gestation dexamethasone alters baroreflex and vascular responses in newborn lambs before hypertension

2006 ◽  
Vol 291 (2) ◽  
pp. R481-R488 ◽  
Author(s):  
Jeffrey L. Segar ◽  
Robert D. Roghair ◽  
Emily M. Segar ◽  
Melissa C. Bailey ◽  
Thomas D. Scholz ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Vascular Reactivity ◽  
Systemic Hypertension ◽  
Arterial Baroreflex ◽  
Vascular Responses ◽  
Early Gestation ◽  
Arterial Blood

Exposure of the early gestation ovine fetus to exogenous glucocorticoids induces alterations in postnatal cardiovascular physiology, including hypertension. To determine whether autonomic function and systemic vascular reactivity are altered by in utero programming before the development of systemic hypertension, we examined arterial baroreflex function and in vivo hemodynamic and in vitro vascular responses to vasoactive agents in 10- to 14-day-old newborn lambs exposed to early gestation glucocorticoids. Dexamethasone (Dex, 0.28 mg·kg−1·day−1) or saline was administered to pregnant ewes by intravenous infusion over 48 h beginning at 27 days gestation (term 145 days), and lambs were allowed to deliver ( n = 6 in each group). Resting mean arterial blood pressure (MABP; 77 ± 1 vs. 74 ± 3 mmHg) and heart rate (HR; 249 ± 9 vs. 226 ± 21 beats/min) were similar in Dex-exposed and control animals, respectively. The arterial baroreflex curve, relating changes in HR to MABP, was significantly shifted toward higher pressure in the Dex-exposed lambs although no change in the sensitivity (gain) of the response was seen. In vivo changes in blood pressure in response to bolus doses of ANG II (20, 50, and 100 ng/kg) and phenylephrine (2, 5, and 10 μg/kg) were similar in the two groups. However, Dex lambs displayed greater decreases in MABP in response to ganglionic blockade with tetraethylammonium bromide (10 mg/kg; −30 ± 3 vs. −20 ± 3 mmHg, P < 0.05) and greater increases in MABP after nitric oxide synthase blockade with NG-nitro-l-arginine (25 mg/kg; 23 ± 3 vs. 13 ± 2 mmHg, P < 0.05) compared with control lambs. By in vitro wire myography, mesenteric and femoral artery microvessel contractile responses to KCl were similar, whereas responses to endothelin (in mesenteric) and norepinephrine (in femoral) were significantly attenuated in Dex lambs compared with controls. Femoral vasodilatory responses to forskolin and sodium nitroprusside were similar in the two groups ( n = 4). These findings suggest that resetting of the baroreflex, accompanied by increased sympathetic activity and altered nitric oxide-mediated compensatory vasodilatory function, may be important contributors to programming of hypertension.

Abstract 293: Inhibition of Nitric Oxide Synthase Decreases Myocardial Injury Following Hemorrhagic Shock and Resuscitation in Rat Model

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Mona Soliman
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Hemorrhagic Shock ◽  
Contractile Function ◽  
Ex Vivo ◽  
Left Ventricular ◽  
Arterial Blood ◽  
Myocardial Contractile ◽  
Oxide Synthase

Resuscitation following hemorrhagic shock result in myocardial contractile dysfunction and injury. We examined the protective effects of non-selective inhibitor of nitric oxide synthase N(G)-nitro-L-arginine methylester (L-NAME) on myocardial contractile function in the isolated perfused hearts, after ex vivo as well as in vivo treatment with L-NAME and resuscitation following one hour of hemorrhagic shock.Male Sprague Dawley rats (300-350 gm) were assigned to 2 sets of experimental protocols: ex vivo and in vivo treatment and resuscitation. Each set has 3 experimental groups (n= 6 per group): normotensive (N), hemorrhagic shock and resuscitation (HS-R) and hemorrhagic shock rats treated with L-NAME and resuscitated (HS- L-NAME-R). Rats were hemorrhaged over 60 min to reach a mean arterial blood pressure of 40 mmHg. In the ex vivo group, hearts were harvested and ex vivo treated and resuscitated by perfused in the Langendorff System. In the L-NAME treated group, L-NAME was added for the first 5 min . Cardiac function was measured Left ventricular generated pressure and +dP/dt were calculated. In the in vivo group, rats were treated with L-NAME intra-arterially after 60 min hemorrhagic shock. Resuscitation was performed in vivo by the reinfusion of the shed blood for 30 min to restore normo-tension. Inhibition of nitric oxide synthase using L-NAME before resuscitation in ex vivo treated and resuscitated isolated hearts and in in vivo treated and resuscitated rats following hemorrhagic shock improved myocardial contractile function. Left ventricular generated pressure and + dP/dt max was significantly higher in L-NAME treated rats compared to the untreated group.Treatment with L-NAME improved left ventricular generated pressure following hemorrhagic shock in the ex vivo as well as the in vivo treated and resuscitated rats. The results indicate that L-NAME protects the myocardium against dysfunction by inhibiting NOS.

scholarly journals Red Blood Cell and Endothelial eNOS Independently Regulate Circulating Nitric Oxide Metabolites and Blood Pressure

Circulation ◽  
2021 ◽  
Author(s):  
Francesca Leo ◽  
Tatsiana Suvorava ◽  
Sophia K. Heuser ◽  
Junjie Li ◽  
Anthea LoBue ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Endothelial Cells ◽  
Vascular Function ◽  
Ex Vivo ◽  
Knock Out ◽  
Catalytically Active ◽  
Nitric Oxide Metabolites ◽  
Plasma Nitrite

Background: Current paradigms suggest that nitric oxide (NO) produced by endothelial cells (ECs) via endothelial nitric oxide synthase (eNOS) in the vessel wall is the primary regulator of blood flow and blood pressure. However, red blood cells (RBCs) also carry a catalytically active eNOS, but its role is controversial and remains undefined. This study aimed to elucidate the functional significance of red cell eNOS compared to EC eNOS for vascular hemodynamics and NO metabolism. Methods: We generated tissue-specific "loss-" and "gain-of-function" models for eNOS by using cell-specific Cre-induced gene inactivation or reactivation. We created two founder lines carrying a floxed eNOS (eNOS flox/flox ) for Cre-inducible knock out (KO), as well as gene construct with an inactivated floxed/inverted exon (eNOS inv/inv ) for a Cre-inducible knock in (KI), which respectively allow targeted deletion or reactivation of eNOS in erythroid cells (RBC eNOS KO or RBC eNOS KI mice) or endothelial cells (EC eNOS KO or EC eNOS KI mice). Vascular function, hemodynamics, and NO metabolism were compared ex vivo and in vivo . Results: The EC eNOS KOs exhibited significantly impaired aortic dilatory responses to acetylcholine, loss of flow-mediated dilation (FMD), and increased systolic and diastolic blood pressure. RBC eNOS KO mice showed no alterations in acetylcholine-mediated dilation or FMD but were hypertensive. Treatment with the NOS inhibitor L-NAME further increased blood pressure in RBC eNOS KOs, demonstrating that eNOS in both ECs and RBCs contributes to blood pressure regulation. While both EC eNOS KOs and RBC eNOS KOs had lower plasma nitrite and nitrate concentrations, the levels of bound NO in RBCs were lower in RBC eNOS KOs as compared to EC eNOS KOs. Crucially, reactivation of eNOS in ECs or RBCs rescues the hypertensive phenotype of the eNOS inv/inv mice, while the levels of bound NO were restored only in RBC eNOS KI mice. Conclusions: These data reveal that eNOS in ECs and RBCs contribute independently to blood pressure homeostasis.

Effects of Neuroactive Amino Acids Derivatives on Cardiac and Cerebral Mitochondria and Endothelial functions in Animals Exposed to Stress

2017 ◽  
Vol 2 (2) ◽  
pp. 34
Author(s):  
TA Popova ◽  
II Prokofiev ◽  
IS Mokrousov ◽  
Valentina Perfilova ◽  
AV Borisov ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Platelet Aggregation ◽  
Atp Synthesis ◽  
Elevated Concentration ◽  
Blood Pressure Monitor ◽  
Pressure Monitor ◽  
Griess Reagent ◽  
Arterial Blood ◽  
Endothelial Functions

Introduction: To study the effects of glufimet, a new derivative of glutamic acid, and phenibut, a derivative of γ-aminobutyric acid (GABA), on cardiac and cerebral mitochondria and endothelial functions in animals following exposure to stress and inducible nitric oxide synthase (iNOS) inhibition. Methods: Rats suspended by their dorsal cervical skin fold for 24 hours served as the immobilization and pain stress model. Arterial blood pressure was determined using a non-invasive blood pressure monitor. Mitochondrial fraction of heart and brain homogenates were isolated by differential centrifugation and analysed for mitochondrial respiration intensity, lipid peroxidation (LPO) and antioxidant enzyme activity using polarographic method. The concentrations of nitric oxide (NO) terminal metabolites were measured using Griess reagent. Hemostasis indices were evaluated. Platelet aggregation was estimated using modified version of the Born method described by Gabbasov et al., 1989. Results: The present study demonstrated that stress leads to an elevated concentration of NO terminal metabolites and LPO products, decreased activity of antioxidant enzymes, reduced mitochondrial respiratory function, and endothelial dysfunction. Inhibition of iNOS by aminoguanidine had a protective effect. Phenibut and glufimet inhibited a rise in stress-induced nitric oxide production. This resulted in enhanced coupling of substrate peroxidation and ATP synthesis. The reduced LPO processes caused by glufimet and phenibut normalized the endothelial function which was proved by the absence of average daily blood pressure (BP) elevation episodes and a significant increase in platelet aggregation level. Conclusion: Glufimet and phenibut restrict the harmful effects of stress on the heart and brain possibly by modulating iNOS activity.

Sign in / Sign up

Export Citation Format

Share Document