Role Of L-arginine Research Articles

The role of L-arginine as a donor of nitric oxide and the prospects for its use: the review

The article discusses recent research on the effective and safe use of the amino acid L-arginine for medicinal purposes in various pathologies. The practical significance of using L-arginine as a source of nitric oxide is considered. The physiological role of nitric oxide, the main vasodilator, was shown, and its deficiency was found to be a key link in endothelial dysfunction. An analysis of modern studies confirming the effectiveness of L-arginine as a donor of nitric oxide was carried out. Ample evidence suggests that oral administration of L-arginine, within physiological limits, can benefit human health by increasing NO synthesis and hence tissue blood flow.

PREGNANT WOMEN STRUGGLING WITH HIGH BLOOD PRESSURE AND STRESS IN PREGNANCY AND ROLE OF NITRIC OXIDE SUPPLEMENTS L-ARGININE FOR PROLONG PERIOD

INTRODUCTION: Mental stress can contribute to the exacerbation of hypertension in pregnant women and preeclampsia by the release of stress hormones such as adrenaline and cortisol level. Less nitric oxide (NO)-dependent vasodilation and excess formation of reactive oxygen species could explain poor placenta perfusion already in PIH and Preeclampsia due to impaired endothelial function. Studies have indicated that Nitric oxide supplement L-arginine can lead to beneficial effects on various cardiometabolic markers, including blood pressure and vascular function especially in pregnant mothers. OBJECTIVE: The primary objective of this meta-analysis study of placebo-controlled trials was to assess and ascertain the evidence of effectiveness of L-arginine and its use in enhancing nitric oxide synthesis to translate into tangible improvement in Hypertension and preeclampsia management, Nitric oxide supplement L-arginine’s ubiquitous molecule’s role is a subject of debate and research with focus on both systolic and diastolic values, pregnancy outcomes and understanding of its role in Hypertension resistant to currently available therapies. METHODS: In this study focused on role of L-arginine on high blood pressure during pregnancy, we did a thorough research, effective communication of information from relevant and up-to-date research articles, studies from reputable sources and great places of academic database like PubMed, Google Scholar, medical journals. Around 16 trials were searched in Pub-Med and Google scholar. A total of six trials were included in this meta-analysis. RESULTS: Result of this meta-analysis shows Nitric Oxide L-arginine supplementation showed a mean decrease in diastolic blood pressure and can lead to beneficial effect on blood pressure and vascular function especially in pregnant mothers with stress, mean increase up to 1. 23 weeks (p = 0. 002) for gestation period to delivery but did not showed reduction in systolic blood pressure as compared to placebo. CONCLUSION: This meta-analysis study supports the notion that availability of this substrate for NO synthesis prolongs the latency to development of preeclampsia and decrease the hypertension in a high-risk pregnant woman with Hypertension and stress.

The role of L-arginine in the pathogenesis of essential arterial hypertension

The role of arginine in the development of primary arterial hypertension continues to be clarified up to the present moment. During natural metabolic processes in cells, methylated forms of arginine are produced – symmetric (SDMA) and asymmetric (ADMA) dimethylarginine. ADMA is a nitric oxide synthase inhibitor and is now considered a well-established marker for endothelial dysfunction. SDMA is not a nitric oxide synthase inhibitor, but may indirectly reduce nitric oxide production through competitive interaction with cellular L-arginine.Currently, arginine preparations are practically not used for the treatment of primary arterial hypertension. This was the rationale for the given scientific review. The article summarizes the information available in the literature (2018–2022) on the pathogenetic mechanisms of the relationship between arginine and the development of impaired vascular tone. We used PubMed and RSCI databases for our review. Using keywords, 1784 publications were found over the past 5 years. The final selection criteria were time frame and matching keywords. The review provides data on the increased ADMA concentrations in experimental hypertensive animals and individuals with essential hypertension. The role of arginine metabolites in the genesis of endothelial dysfunction and arterial hypertension and the prospects for the therapeutic use of this compound are discussed.

The Emerging Role of Prediabetes and Its Management: Focus on L-Arginine and a Survey in Clinical Practice.

The worldwide impressive growth of metabolic disorders observed in the last decades, especially type 2 diabetes mellitus and obesity, has generated great interest in the potential benefits of early identification and management of patients at risk. In this view, prediabetes represents a high-risk condition for the development of type 2 diabetes mellitus and cardiovascular diseases, and an ideal target to intercept patients before they develop type 2 diabetes gaining a prominent role even in international guidelines. For prediabetic individuals, lifestyle modification is the cornerstone of diabetes prevention, with evidence of about 50% relative risk reduction. Accumulating data also show potential benefits from pharmacotherapy. In this context, the only available data pertain to metformin as a pharmaceutical drug and vitamin D and L-arginine as nutraceuticals. L-arginine appears to be a very interesting tool in the clinical management of patients with pre-diabetes. In this review we summarize the current knowledge on the role of L-arginine in prediabetes as a potentially useful preventive strategy against the progression to type 2 diabetes, with a particular focus on the underlying molecular mechanisms and the past and ongoing trials. In this article we also report the interesting data about the perception of the prediabetic condition and its therapeutic management in the clinical practice in Italy. An early identification and a prompt management of people with prediabetes appears to be of paramount importance to prevent the progression to diabetes and avoid its cardiovascular consequences.

Abstract 3696: L-arginine depletion causes different proliferation responses in breast cancer subtypes - Relation to gene expression profiles of L-arginine metabolic pathways

Abstract Metabolic fingerprinting provides insight into cancer biology, improving personalized therapeutic strategies. We sought to unravel responses of the molecular subtypes of breast cancer to L-arginine depletion in vitro. Availability of the semi-essential amino acid L-arginine limits protein synthesis and cell proliferation. L-Arginine is the substrate for nitric oxide synthases (NOS) and arginases (ARG), enzymes also involved in the regulation of cell proliferation. Clinical studies have provided contrasting results regarding the role of L-arginine in breast cancer.We studied the response of different breast cancer cell lines to L-arginine depletion and the molecular mechanisms underlying this effect. MCF-7, SK-BR-3, BT-474, MDA-MB-231, and MDA-MB-468 cells were cultured under standard conditions and compared to MCF-12A normal breast epithelial cells. Cells were maintained in culture media with 200 mg/L (control) or 0 mg/L of L-arginine (depletion) for up to 240 h. Cell proliferation was analyzed and intracellular concentrations of L-arginine, L-ornithine, and L-citrulline were measured by UPLC-MS/MS every 24 h. mRNA expression of genes involved in L-arginine metabolism was quantified by qRT-PCR. MCF-12A control cells did not proliferate in the absence of extracellular L-arginine. Their intracellular L-arginine content dropped sharply, whilst L-ornithine and L-citrulline were only slightly reduced. By contrast, proliferation of BT-474, SK-BR-3, and MDA-MB-468 cells was unaffected by L-arginine depletion (p<0.05), whilst MCF-7 and MDA-MB-231 cells showed significantly higher proliferation rates in the absence of L-arginine (p<0.05). L-arginine concentration dropped sharply within 24 h in MCF-7 cells, but only by 25-50% in the other cell lines (p<0.01). L-ornithine dropped to almost zero within 24 h in both estrogen receptor positive cell lines (MCF-7 and BT-474), whilst being only slightly reduced in SK-BR-3 cells (p<0.01). L-ornithine was not significantly reduced in MDA-MB-231, but strongly reduced in MDA-MB-468 cells (p<0.05). L-citrulline showed no significant change in any of the cell lines. mRNA expression of NOS, ARG, and the L-arginine salvage pathway (ASS1 and ASL) was differentially expressed amongst the cell lines. SK-BR-3 showed high expression of the L-arginine salvage pathway; BT-474 had the highest expression levels of NOS and ARG2, and MDA-MB had high ARG2 but very low NOS expression. Gene expression patterns of MCF-12A and MCF-7 were very similar. In conclusion, metabolic fingerprinting reveals complex and differential regulation of L-arginine pathways in breast cancer cell lines. These analyses may help to understand differences in proliferation during L-arginine depletion, thus offering a perspective to further personalize treatment options within classical molecular breast cancer subtypes. Citation Format: Juliane Hannemann, Fiona Franke, Mariola Kastner, Rainer Böger. L-arginine depletion causes different proliferation responses in breast cancer subtypes - Relation to gene expression profiles of L-arginine metabolic pathways. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3696.

Treatment optimization of the age-related cardiovascular and neurological pathology using known metabolic, cytoprotective, vasodilatory action substances. Review

Stressful situations that accompany us during military operations provoke a significant increase in the incidence of cardiovascular and psychoneurological pathology, especially among the elderly. Therefore, there is a need for a complex approach to treatment, in particular, with the use of combined drugs. The review presents data from preclinical and clinical studies on drugs with metabolic action - meldonium (trimethylhydrazinium propionate), L-arginine, and inosine. It has been shown that, apart from the general pharmacotherapeutic action, these drugs have a significant clinical effect on various illnesses in the form of adjunctive therapy. Antioxidant, neuroprotective, vasodilatory, and several pleiotropic effects of meldonium have been established. The use of meldonium as part of combined therapy improves the prognosis in cardiovascular and neurological disease treatment. Most reports ascribe the clinical benefits of L-arginine in cardiovascular diseases to the provision of NO. L-arginine is the only precursor for the NO-synthase reaction. NO is produced by all tissues of the body and plays particularly important roles in cardiovascular homeostasis. Very few articles examine the effects of L-arginine supplementation on central nervous system (CNS) function. However, accumulating evidence indicates that NO plays a role in memory formation. The possible role of L-arginine in Alzheimer's disease was investigated, taking into account the known functions of L-arginine in atherosclerosis, redox stress and inflammation, regulation of synaptic plasticity and neurogenesis, as well as modulation of glucose metabolism and insulin activity. Evidence is provided that L-arginine may play a prominent role in protecting against age-related degenerative diseases such as Alzheimer's disease. L-arginine has been demonstrated to improve peripheral circulation, renal function, and immune function. It also possesses anti-stress and adaptogenic capabilities. L-arginine stimulates the release of growth hormone as well as the release of pancreatic insulin and glucagon and pituitary prolactin. The antioxidant property of L-arginine has been well documented in several reports. As well known that inosenhancesance the myocardial energy potential improvesrove coronary circulation. At the same time over the past two decades, inosine has been shown to evoke significant improvements in motor function and visceral organ control in preclinical models of neurologic injury including spinal cord injury, stroke, traumatic brain injury, multiple sclerosis, and Parkinson`s disease through its ability to enhance the growth of axon collaterals from undamaged neurons. The basis of these beneficial effects stems from its antioxidant, anti-inflammatory, anxiogenic and neuroprotective properties. Keywords: age-related pathology; combined drugs; meldonium; L-arginine; inosine, endothelial dysfunction.

Comparative evaluation of the effect of L-Arginine and L-Homoarginine supplementation on reproductive physiology in ewes

L-Arginine (LA) is a well-known amino acid involved in vital physiological processes. However, the physiological function of its methylated form known as L-Homoarginine (LHA), is not well understood. The aim of this study was to study the comparative effects of LA and LHA treatment on selected metabolites and parameters of reproductive physiology in non-pregnant ewes. Twelve Deccani ewes were selected and randomly distributed into 3 groups: Control, LA treated group and LHA group. Blood samples were collected for the evaluation of blood indices and hormone levels. Overall, nitrite, ovary weight, surface follicle number, estrogen, insulin like growth factor-1 (IGF-1), vascular endothelial growth factor (VEGF) showed an increase in the LA and LHA treated animals. On the other side, the levels of progesterone, inteleukin-1 beta (IL-1β), IL-6, tumor necrosis factor-alpha (TNF-α) were found to be decreased in LA and LHA group. Ovary size was not affected by LA and LHA treatment groups. In comparison with LA, the ovary weight, surface follicle number, estrogen levels and IL-6 expression were higher in LHA treated animals. The expression of VEGF indicated improved angiogenesis in the treated animals. Further, the expression of heat shock protein-27 (HSP-27) and HSP-70 were differentially modulated by LA and LHA. This data reinforces the beneficial role of LA and its metabolites LHA on the ovarian physiology and functionality and also reveals the potent role of LHA as an alternative to LA treatment in enhancing the reproductive ability in non-pregnant ewes.

The Future of L-Arginine Dietary Supplementation Research - The Impact on NOS Dependent and Independent Systems

Introduction: The consumption of L-arginine is of particular concern, due to the importance of dietary supplements in people’s daily life, continually increasing. Also, the counter position is the impact of adulterants, contaminants and undeclared constituents in L-arginine products, and consequently to health/wellness. Aim: To contextualize and provide new perspectives for L-arginine dietary supplement research, that would have an impact on the consumers, and patients, health/wellness. Method: The approach was to do a literature search in multiple online electronic academic open-source scientific databases. These covered, PubMed, Scopus, Google Scholar, Elsevier, Taylor & Francis, Sabinet, ScienceDirect, ClinicalTrials.gov, and The Cochrane Collaboration. The search terms covered  L-arginine, and the specific research related interest. Outcome: The role of L-arginine in inhibition and control of disease is essentially via the dependent or independent NO metabolic pathways. In L-arginine deficiency, the selective delivery is exogenously taking the amino acid. That there is an impact of dietary arginine containing supplements consumption (or in combination) on human performance (exercise), including effects on cognitive flexibility, and/or mental ability. That L-arginine supplementation is indicated for stress reduction, anxiety, and adaptogenic capabilities in the healthy. However, L-arginine is not lacking, in side effects, including drug-interactions when taken in combination. Gastrointestinal disturbances being the most common adverse effects. Conclusion: Of prominence is the potential benefit, pure L-arginine holds for the consumer. It is recommended that further scientific research scrutiny is warranted. This will provide awareness for an improved specific national regulatory framework, globally, but also set the tone for future research studies.

Cluster Model Study into the Catalytic Mechanism of α-Ketoglutarate Biodegradation by the Ethylene-Forming Enzyme Reveals Structural Differences with Nonheme Iron Hydroxylases

Ethylene is an important signaling molecule in plants that triggers the growth of leaves, flowers, and fruits. One of the enzymes involved in the biosynthesis of ethylene is the ethylene-forming enzyme (EFE), which is an usual nonheme iron enzyme that biodegrades α-ketoglutarate into three CO2 molecules and ethylene. As the detailed mechanism of EFE in the biosynthesis of ethylene remains controversial and particularly the function of the co-substrate l-arginine, we decided to pursue a density functional theory study on the possible pathways of the enzyme leading to ethylene biosynthesis and test many possible pathways and mechanisms. A large active site cluster model of 322 atoms was created, which contains all the features of the first- and second-coordination sphere of the active site and substrate (α-ketoglutarate) binding pockets. The calculations identify a persuccinate intermediate that triggers a bifurcation pathway in the enzyme and either react with a molecule of CO2 to form a carbonate or forms a high-valent iron(IV)-oxo species through heterolytic dioxygen bond cleavage. Our studies show that both the bifurcation pathways converge to the same intermediate again and can lead to ethylene products, although the two pathways have different kinetics. Interestingly, our studies also show that the iron(IV)-oxo itself can form a carbonate and ethylene but through much higher barriers. As a matter of fact, these barriers are higher in energy than the typical aliphatic hydroxylation barriers and may not be competitive with arginine hydroxylation. Inclusion of the l-arginine co-substrate into the model leads to minor changes in the structure and fold, but its charge and dipole moment does not seem to affect the first stage of the catalytic cycle. Moreover, the key activation barriers seem less affected by the inclusion of l-arginine into the model. We, therefore, believe that the role of l-arginine is to lock α-ketoglutarate and its products into a tight binding pocket to enable its degradation and to prevent early release of CO2. Our studies show that due to the distinct differences in α-ketoglutarate positioning between different arginine activating nonheme iron dioxygenases in the co-substrate binding pocket and its tighter binding in EFE, we predict that the release of CO2 is prevented in the first stage of the oxygen activation mechanism. This enables attack of CO2 on a persuccinate complex to form carbonate products, leading to ethylene formation. This work gives suggestions on the engineering of EFE into a hydroxylase or improving the ethylene biosynthesis.

Role of l-arginine in the prevention of pre eclampsia in high-risk pregnancies.

Objective: To compare the efficacy of L-Arginine versus placebo in the prevention of pre eclampsia in high-risk pregnancies. Study Design: Randomized Control Trial. Setting: Department of Obstetrics and Gynecology, Nishtar Hospital Multan. Period: November 2019 to February 2019. Material & Methods: A total of 130 women were included in the study. 65 patients were in L-arginine group or Group A while 65 patients were in placebo group or Group B. In group A, women were prescribed L-arginine 300 grams (Amino Whey Sachet) once a day until delivery and in group B; women were given homologated placebo (starch) once a day until delivery. Efficacy (no preeclampsia occurs during pregnancy) was noted from both groups and recorded. Mean ±SD was presented for quantitative variables like age, gestational age, parity, duration of chronic hypertension, weight, height and BMI. Variables such as age, parity, hypertension, body mass index, gestational age and duration of hypertension were stratified to assess their effect on efficacy. Chi square test was used to make comparison of the efficacy in both groups as well as for post-stratification for both groups. A p value of less than or equal to 0.05 was taken as significant. Results: In L-arginine group efficacy was 92.3% as compared to 69.2% in placebo group (p< 0.000) Table-IV. Conclusion: It can be concluded that L-arginine when given orally at the dose of 300g daily has a considerable role in prevention of pre-eclampsia in pregnant patients with high risk and also has a role in reduction of severity of pre-eclampsia.

The Effects of L-Arginine in Hypertensive Patients: A Literature Review.

Hypertension (HTN) is a chronic disease that affects more than 972 million people throughout the world, which is usually associated with endothelial dysfunction. Scientists are closely investigating endothelial dysfunction and have recently discovered the endothelium-derived relaxing factor (EDRF) known as NO (nitric oxide), which is derived from a semi-essential amino acid, L-arginine, by the action of endothelial nitric oxide synthase (eNOS). Production of adequate amounts of NO by vascular endothelial cells is essential to maintain normal blood pressure and prevent the development of HTN. Asymmetrical dimethylarginine (ADMA) is an endogenous NOS inhibitor that is increased in those with HTN especially in patients with renal dysfunction. In the present review, the role of L-arginine, arginine transporters, and ADMA in the pathobiology of HTN and their potential clinical significance are discussed.

Modulatory Effects of L-Arginine on Methylxanthine-Induced Cardiotoxicity in Rats: A Differential Role for Nitric Oxide (NO)

Methylxanthines are potent bronchodilators used in obstructive airway disease like COPD and bronchial asthma, but the narrow therapeutic index and resultant adverse effect profile have restricted their use. Novel beneficial effects and modes of action are now being proposed for these pharmacoeconomically viable agents. Cardiotoxicity is a prominent adverse effect of methylxanthone and thus we investigated possible mechanisms for such toxicity with an aim to devise ameliorative strategies for counteracting such undesirable effects. In view of the cardioprotective role of nitric oxide (NO) and NO mimetics, the present study investigated the possible modulatory role of L-arginine, a NO precursor, in theophylline induced cardiotoxicity in rats, with a view to exploring strategies for facilitating the safe use of this drug. The methylxanthine, aminophylline induced cardiotoxic effects like increased heart rat, raised mean BP, inverted T-waves and prolonged QTc interval (in ECG). These were accompanied by increased levels of cardiac biomarkers like Troponin-I, CPK-MB, and ADMA. Oxidative stress markers like MDA were elevated whereas, antioxidant defence markers like GSH and SOD were suppressed. Co-administration of L-arginine (with aminophylline) had dose-related effects on cardiac function (heart rate, mean BP, ECG changes) and cardiospecific biomarkers (TnI, CPK-MB, ADMA) - the lower dose being protective whereas the higher dose potentiating some of the cardiac effects and cardiospecific/oxidative stress biomarker levels. The results indicate a biphasic involvement of NO in the cardiotoxic effect of theophylline and suggests possible interactions of NO with reactive oxygen species during such modulations of cardiotoxicity.

Role of L-arginine on the formation and breakdown of passive film onto the steel rebars surface in chloride contaminated concrete pore solution

In the present study, different amounts of L-arginine (LA) i.e. Zwitterion have been used as an eco-friendly corrosion inhibitor to study its effect on the mitigation of the steel rebars corrosion in 0.17 M NaCl added simulated concrete pore (SP) solution. Potentiodynamic polarization, open circuit potential (OCP), and electrochemical impedance spectroscopy (EIS) have been used to understand the corrosion kinetics and mechanism for the formation of passive film at steel rebar/solution interface with exposure periods. The characterization of passive films after 144 h of exposures were performed by scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS), and Raman spectroscopy. Cl− ions help in the formation of Zwitterion-(Cl)-Fe complex in the presence of LA containing solution which led to stabilize the passive film resulting improvement in polarization resistance (Rp). The steel rebar exposed to 0.115 M LA containing SP + 0.17 M NaCl solution exhibited around 96% inhibition efficiency after 144 h of exposure. Raman spectroscopy of passive film reveals adsorption of LA and formation of goethite and maghemite. A schematic has been proposed to derive the adsorption mechanism of LA in the presence of Cl− ions and form Zwitterion-(Cl)-Fe complex, therefore, enhanced corrosion resistance was observed.

Long lasting protective effects of early l-arginine treatment on endothelium in an in vitro study

Excess nutrient supply, such as high fat and high glucose intake, promotes oxidative stress and advanced glycation end products accumulation. Oxidative stress and AGE accumulation cause pathological elevation of arginase activity and pro-inflammatory signaling implicated in endothelial dysfunction. Several studies showed positive effects of l-arginine supplementation in endothelial function but little is currently known about the role of l-arginine as prevention of endothelial dysfunction caused by excessive nutrient supply (overfeeding). Our aim was to evaluate a possible protective effect of l-arginine on endothelial dysfunction caused by excessive nutrient supply (overfeeding), using human endothelial cells line in an invitro study. Endothelial EA.hy926cells were pre-treated with 1.72mM of l-arginine for 24h and afterwards subjected to nutritional stress (high lipid, high insulin and high glucose concentrations) for further 24h. After treatment discontinuation, the cells were kept in culture for 48h, in physiological condition, to evaluate the effects of treatments after normalization. Excess nutrient supply in EA.hy926cell line showed an increase of oxidative and nitrosative stress, a rise of AGEs production, high arginase activity, leading the cells to acidosis and to cell death. l-arginine pretreatment protects the cells by reducing apoptosis, acidosis, oxidative and nitrosative stress, arginase activity and AGE accumulation. l-arginine pretreatment reduces AGEs generation and accumulation by regulating STAB1 and RAGE gene expression levels. STAB1, acting as receptor scavenger of AGEs, interferes with AGE-RAGE binding and thus prevents activation of intracellular signaling pathways leading to cell damage. Moreover the reduction of oxidative stress promotes a decrease of excessive activation of arginase involved in endothelial dysfunction. The effects of pretreatment with l-arginine last even in the absence of stimuli and despite after treatment discontinuation. An early l-arginine treatment is able to prevent oxidative stress and AGEs accumulation caused by overfeeding in human endothelial cell line by regulating STAB1/RAGE gene expression and by reducing excess arginase activity. The positive effects of l-arginine pretreatment continue even after treatment discontinuation in normal conditions.

Relaxation of Goat Detrusor Muscle by L-arginine Involves NO-dependent but Guanylyl Cyclase Independent Activation of KCa Channels

Background: Urinary incontinence is a major problem both in man and animals particularly dogs. L-arginine, the precursor of NO, relaxes coronary artery smooth muscle by opening of KATP channels. L-arginine has beneficial circulatory effects in patients with essential and secondary hypertension. However, not much is known about the role of L-arginine on bladder physiology. In view of this, the present work investigated the functional role of L- arginine on detrusor smooth muscle of goat. Methods: Detrusor strips of goat, collected from local abattoir were mounted in a thermostatically controlled (37° ± 0.5°C) organ bath (20 ml capacity) containing physiological solution. After 1 hr of equilibrium, carbachol (CCh) (10-5 M) was used to induce sub-maximal contraction. L-arginine (10-3 M) was added at the plateau of contraction to see any observable effect in absence and presence of modulators of NO and ion channels. Result: L- arginine (10-3 M) reversed the contractions induced by CCh (10-5 M) on detrusor tissues. Methylene blue (MB) (10-5 M), the non-specific guanylyl cyclase inhibitor, failed to attenuate the relaxant response of L-arginine but, the NO synthase inhibitor L-NAME (3 x 10-6 M) inhibited the relaxant response of L-arginine. The KATP channel blocker glibenclamide (10-6 M) failed to inhibit the relaxation induced by L-arginine while KCa channel blocker tetraethylammonium (TEA) (10-3 M) inhibited the relaxant response of L-arginine. The results of the present study suggest that L-arginine produces relaxation of goat detrusor muscle and the L-arginine-elicited relaxation is NO-dependent but guanylyl cyclase independent which activates KCa channels.

Role of L-Arginine in Nitric Oxide Synthesis and Health in Humans.

As a functional amino acid (AA), L-arginine (Arg) serves not only as a building block of protein but also as an essential substrate for the synthesis of nitric oxide (NO), creatine, polyamines, homoarginine, and agmatine in mammals (including humans). NO (a major vasodilator) increases blood flow to tissues. Arg and its metabolites play important roles in metabolism and physiology. Arg is required to maintain the urea cycle in the active state to detoxify ammonia. This AA also activates cellular mechanistic target of rapamycin (MTOR) and focal adhesion kinase cell signaling pathways in mammals, thereby stimulating protein synthesis, inhibiting autophagy and proteolysis, enhancing cell migration and wound healing, promoting spermatogenesis and sperm quality, improving conceptus survival and growth, and augmenting the production of milk proteins. Although Arg is formed de novo from glutamine/glutamate and proline in humans, these synthetic pathways do not provide sufficient Arg in infants or adults. Thus, humans and other animals do have dietary needs of Arg for optimal growth, development, lactation, and fertility. Much evidence shows that oral administration of Arg within the physiological range can confer health benefits to both men and women by increasing NO synthesis and thus blood flow in tissues (e.g., skeletal muscle and the corpora cavernosa of the penis). NO is a vasodilator, a neurotransmitter, a regulator of nutrient metabolism, and a killer of bacteria, fungi, parasites, and viruses [including coronaviruses, such as SARS-CoV and SARS-CoV-2 (the virus causing COVID-19). Thus, Arg supplementation can enhance immunity, anti-infectious, and anti-oxidative responses, fertility, wound healing, ammonia detoxification, nutrient digestion and absorption, lean tissue mass, and brown adipose tissue development; ameliorate metabolic syndromes (including dyslipidemia, obesity, diabetes, and hypertension); and treat individuals with erectile dysfunction, sickle cell disease, muscular dystrophy, and pre-eclampsia.

Preconception preparation for pregnancy

Background. Experience in high-risk obstetrics shows that a significant part of the determining factors affects the woman and the fetus before the first visit to the doctor. Improving a woman’s health before conception can improve her reproductive performance and reduce financial costs spent on obstetric medical aid.
 Objective. Describe the key concepts of preconception training.
 Materials and methods. Analysis of literature sources on this topic; own study involving 42 pregnant women (22 women with systemic lupus erythematosus (SLE), 20 women with congenital heart disease (CHD) and hypertensive complications of previous pregnancies), who were divided into two groups. Group 1 received routine drugs and L-arginine (Tivortin, “Yuria-Pharm”) in doses recommended for cardiac patients, and group 2 – only routine drugs.
 Results and discussion. The components of preconception programs include the individual responsibility of women throughout life, awareness of women, preventive visits, interventions on identified risks, pre-pregnancy examinations and pregnancy supervision, health insurance for low-income women, health programs and strategies, medical research, and the improvement of monitoring. Target groups of preconception include women with unfavorable obstetric history (premature birth, cessation of fetal development, cesarean section, stillbirth, multiple miscarriages, birth of children with birth defects, hypertensive complications of pregnancy) and chronic diseases (type 1 diabetes mellitus, SLE, antiphospholipid syndrome, severe cardiovascular pathology, arterial hypertension, pulmonary hypertension). An important role in the management of pregnant women belongs to the prevention of preeclampsia (PE). Administration of acetylsalicylic acid reduces the likelihood of PE by 10 % in low-risk pregnant women and by 25 % in high-risk pregnant women, but the drug should be started during gestation. The use of calcium (1000 mg) reduces the risk of PE in high-risk pregnant women by 37 %. Preconception preparation is especially important, because some processes, such as the implantation of placental structures, begin and end before a woman learns she is pregnant. Remodeling of the spiral arteries also begins in the early stages of pregnancy, so its correction after the confirmation of pregnancy is less effective than prevention before it occurs. E.E. Camarena Pulido et al. (2016) studied the role of L-arginine (5 tablets of 600 mg per day from the 20th week of gestation before delivery) in the prevention of PE in high-risk women. In the L-arginine group significantly fewer cases of PE (3/49 vs. 11/47 in the placebo group; p=0.01) and a lower incidence of preterm birth were detected. In the another study, pregnant women with chronic hypertension received oral L-arginine or placebo. In the arginine group, there was a lower need for antihypertensive drugs, as well as lower frequency of births before 34 weeks, PE and neonatal complications (Neri I. et al., 2010). In the own study, favorable obstetric results of Tivortin were found. The percentage of births at >37 weeks in the Tivortin group among women with SLE was 90.9 %, and in the group of standard therapy – 50 % (p<0.01), among women with CHD – 90 % and 75 % respectively; p<0.05). No newborns with an Apgar score of <7 were found in the Tivortin group. In the comparison group their number was 27.7 %. Laboratory studies have shown that there is a significant increase in endothelial progenitor cells in the Tivortin group.
 Conclusions. 1. Preconception preparation of pregnant women is a multifaceted set of measures. 2. A significant number of physiological and pathological processes occur in the early stages of pregnancy, so they can be influenced only in the preconception period. 3. The use of L-arginine during gestation reduces the risk of PE, premature birth and other complications in all women and especially in women with hypertension.

Heterologous expression, purification, and refolding of SRY protein: role of L-arginine as analyzed by simulation and practical study.

Escherichia coli is a widely-used cell factory for recombinant protein production, nevertheless, high amount of produced protein is seen in aggregated form. The purpose of this study was to improve the solubility of recombinant bovine sex-determining region Y protein (rbSRY) by exploring the effect of temperature, inducer, and water-arginine mixed solvent. Codon-optimized rbSRY expressed in Rosetta-gami B (DE3) pLysS and purified by NI-NTA His-select affinity chromatography in the native and denaturing conditions. A three-dimensional model of SRY was built and studied through molecular dynamics simulations in water and in the presence of L-arginine as co-solvent. Results indicated the significant effects of temperature and IPTG concentration (P < 0.001) on the solubility of rbSRY. The binding activity of native, inclusion bodies and refolded fractions to anti-rbSRY monoclonal antibody were concentration-dependent (P < 0.001). Based on molecular modeling results, the propensity of fragments in the N-terminal domain to form β-sheet and the relative instability of α-helices in terminal domains are the probable reasons for the high aggregation potential of SRY, which are mitigated in the presence of L-arginine. Altogether, our rbSRY protein was properly produced and applying appropriate culture conditions could help enhance its solubility, refold inclusion bodies, and improve its activity upon refolding.

L-Arginine Ameliorates High-Fat Diet-Induced Atherosclerosis by Downregulating miR-221.

Objectives Atherosclerosis (AS) is a severe disease in which the inside of an artery narrows because of plaque formation, leading to endothelial injury in the patients. Although it has been found that endothelial nitric oxide synthase (eNOS), which produces a low concentration of NO, is necessary for endothelial function and integrity, the regulatory mechanisms of eNOS expression against the pathogenesis and development of AS are unclear. Evidence has indicated that diet supplementation with L-arginine could reduce the size of the endothelial injury lesions in AS patients. In addition, nonencoding microRNAs (miRNAs) were found to be a promising tool that regulates the expression of eNOS in human endothelial cells. Design The aim of this research was to explore the role of L-arginine in the development of AS and the mechanisms by which miR-221 influences the possible signaling pathways in endothelial cells during AS. Results The results suggested that L-arginine could prevent oxidized low-density lipoprotein-induced apoptosis in endothelial cells, which is associated with the downregulation of miR-221. Similar results were also observed in rat AS models. Conclusion This research could provide potential therapies for the treatment of AS.

Role of L-Arginine In Uteroplacental Vascular Insufficiency

Role of L-Arginine In Uteroplacental Vascular Insufficiency