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Citrulline AND microcirculation

Deepak Gopalakrishna, Samantha Pennington, Amel Karaa, Mark G Clemens
It has been shown that microcirculation is hypersensitized to endothelin1 (ET-1) following endotoxin (lipopolysaccharide [LPS]) treatment leading to an increased vasopressor response. This may be related in part to decreased activation of endothelial nitric oxide synthase (eNOS) by ET-1. eNOS can also be uncoupled to produce superoxide (O2). This aberrant eNOS activity could further contribute to the hyperconstriction and injury caused by ET-1 following LPS. We therefore tested whether LPS affects ROS production by vascular endothelial cells and whether and how this effect is altered by ET-1...
July 2016: Shock
Antonin Ginguay, Jean-Pascal De Bandt, Luc Cynober
PURPOSE OF REVIEW: The review assesses the utility of supplementing parenteral or enteral nutrition of ICU patients with each of five specific amino acids that display pharmacological properties. Specifying indications implies also stating contraindications.Combined supplementation of amino acids with ω3-fatty acids and/or trace elements (immune-enhancing diets) will not be considered in this review because these mixtures do not allow the role of amino acids in the effect (positive or negative) of the mixture to be isolated, and so cannot show whether or not supplementation of a given amino acid is indicated...
March 2016: Current Opinion in Clinical Nutrition and Metabolic Care
Karolina A P Wijnands, Dennis M Meesters, Kevin W Y van Barneveld, Ruben G J Visschers, Jacob J Briedé, Benjamin Vandendriessche, Hans M H van Eijk, Babs A F M Bessems, Nadine van den Hoven, Christian J H von Wintersdorff, Peter Brouckaert, Nicole D Bouvy, Wouter H Lamers, Anje Cauwels, Martijn Poeze
Enhanced arginase-induced arginine consumption is believed to play a key role in the pathogenesis of sickle cell disease-induced end organ failure. Enhancement of arginine availability with L-arginine supplementation exhibited less consistent results; however, L-citrulline, the precursor of L-arginine, may be a promising alternative. In this study, we determined the effects of L-citrulline compared to L-arginine supplementation on arginine-nitric oxide (NO) metabolism, arginine availability and microcirculation in a murine model with acutely-enhanced arginase activity...
July 2015: Nutrients
Tyler A Churchward-Venne, Lisa M Cotie, Maureen J MacDonald, Cameron J Mitchell, Todd Prior, Steven K Baker, Stuart M Phillips
Aging is associated with anabolic resistance, a reduced sensitivity of myofibrillar protein synthesis (MPS) to postprandial hyperaminoacidemia, particularly with low protein doses. Impairments in postprandial skeletal muscle blood flow and/or microvascular perfusion with hyperaminoacidemia and hyperinsulinemia may contribute to anabolic resistance. We examined whether providing citrulline, a precursor for arginine and nitric oxide synthesis, would increase arterial blood flow, skeletal muscle microvascular perfusion, MPS, and signaling through mTORC1...
July 1, 2014: American Journal of Physiology. Endocrinology and Metabolism
Kim van Wijck, Karolina A P Wijnands, Dennis M Meesters, Bas Boonen, Luc J C van Loon, Wim A Buurman, Cornelis H C Dejong, Kaatje Lenaerts, Martijn Poeze
PURPOSE: Splanchnic hypoperfusion is a physiological phenomenon during strenuous exercise. It has been associated with gastrointestinal symptoms and intestinal injury and may hamper athletic performance. We hypothesized that L-citrulline supplementation improves splanchnic perfusion and decreases intestinal injury by enhancing arginine availability. The aim of this study was to determine the effect of L-citrulline intake on splanchnic perfusion, intestinal injury, and barrier function during exercise...
November 2014: Medicine and Science in Sports and Exercise
Karolina A P Wijnands, Marten A Hoeksema, Dennis M Meesters, Nynke M S van den Akker, Daniel G M Molin, Jacob J Briedé, Mitrajit Ghosh, S Eleonore Köhler, Marc A M J van Zandvoort, Menno P J de Winther, Wim A Buurman, Wouter H Lamers, Martijn Poeze
RATIONALE AND OBJECTIVE: Arginase-1 is an important component of the intricate mechanism regulating arginine availability during immune responses and nitric oxide synthase (NOS) activity. In this study Arg1(fl/fl)/Tie2-Cre(tg/-) mice were developed to investigate the effect of arginase-1 related arginine depletion on NOS2- and NOS3-dependent NO production and jejunal microcirculation under resting and endotoxemic conditions, in mice lacking arginase-1 in endothelial and hematopoietic cells...
2014: PloS One
Koichiro Homma, Koichi Hayashi, Shu Wakino, Hirobumi Tokuyama, Takeshi Kanda, Satoru Tatematsu, Kazuhiro Hasegawa, Seitaro Fujishima, Shingo Hori, Takao Saruta, Hiroshi Itoh
Renal afferent arterioles (AFF) regulate glomerular capillary pressure through two main mechanisms: the myogenic response (MYO) and tubuloglomerular feedback (TGF). Because Rho-kinase and nitric oxide synthase (NOS) are established factors that modulate vascular tone, we examined the role of these factors in pressure-induced AFF tone in Wistar-Kyoto rats and in spontaneously hypertensive rats (SHR) using an intravital CCD camera. Elevated renal perfusion pressure elicited marked AFF constriction that was partially inhibited by gadolinium, furosemide and fasudil, which inhibit MYO, TGF and Rho-kinase, respectively; however, this AFF constriction was completely blocked by combined treatment with fasudil+gadolinium or fasudil+furosemide...
2014: Keio Journal of Medicine
Carlijn T I de Betue, Nicolaas E P Deutz
Arginine is an important amino acid during disease and healing because of functions in the immune system and as precursor of nitric oxide (NO). In critically ill adults and children, plasma arginine and citrulline concentrations are substantially decreased, indicating an arginine-deficient state. Arginine availability is reduced because of increased arginine disposal in combination with reduced de novo arginine synthesis. The latter is most likely caused by reduced citrulline availability. As a result, NO synthesis may be impaired, which might compromise microcirculation...
2013: Nestlé Nutrition Institute Workshop Series
Daniel M Hirai, Steven W Copp, Clark T Holdsworth, Scott K Ferguson, Timothy I Musch, David C Poole
Advanced age is associated with derangements in skeletal muscle microvascular function during the transition from rest to contractions. We tested the hypothesis that, contrary to what was reported previously in young rats, selective neuronal nitric oxide (NO) synthase (nNOS) inhibition would result in attenuated or absent alterations in skeletal muscle microvascular oxygenation (Po(2)(mv)), which reflects the matching between muscle O(2) delivery and utilization, following the onset of contractions in old rats...
October 15, 2012: American Journal of Physiology. Heart and Circulatory Physiology
Karolina A P Wijnands, Hans Vink, Jacob J Briedé, Ernst E van Faassen, Wouter H Lamers, Wim A Buurman, Martijn Poeze
BACKGROUND: Impaired microcirculation during endotoxemia correlates with a disturbed arginine-nitric oxide (NO) metabolism and is associated with deteriorating organ function. Improving the organ perfusion in endotoxemia, as often seen in patients with severe infection or systemic inflammatory response syndrome (SIRS) is, therefore, an important therapeutic target. We hypothesized that supplementation of the arginine precursor citrulline rather than arginine would specifically increase eNOS-induced intracellular NO production and thereby improve the microcirculation during endotoxemia...
2012: PloS One
Narbeh Melikian, Michael D Seddon, Barbara Casadei, Philip J Chowienczyk, Ajay M Shah
Vascular blood flow and its distribution among different vascular beds are regulated by changes in microvascular tone. Nitric oxide (NO) plays a key role in the local paracrine regulation of vessel tone both under resting conditions and when blood flow increases in response to agonist stimulation or increased shear stress. The conventional notion that endothelial NO synthase (eNOS)-derived NO is largely responsible for both effects has been challenged by first-in-human studies with a selective inhibitor of neuronal NOS (nNOS), S-methyl-l-thiocitrulline (SMTC)...
November 2009: Trends in Cardiovascular Medicine
Dhananjay K Kaul, Xiaoqin Zhang, Trisha Dasgupta, Mary E Fabry
In sickle cell disease, nitric oxide (NO) depletion by cell-free plasma hemoglobin and/or oxygen radicals is associated with arginine deficiency, impaired NO bioavailability, and chronic oxidative stress. In transgenic-knockout sickle (BERK) mice that express exclusively human alpha- and beta(S)-globins, reduced NO bioavailability is associated with induction of non-NO vasodilator enzyme, cyclooxygenase (COX)-2, and impaired NO-mediated vascular reactivity. We hypothesized that enhanced NO bioavailability in sickle mice will abate activity of non-NO vasodilators, improve vascular reactivity, decrease hemolysis, and reduce oxidative stress...
July 2008: American Journal of Physiology. Heart and Circulatory Physiology
J L Sartoretto, R A Santos, C Scavone, R C Tostes, D Nigro, M H C Carvalho, R K N Cuman, Z B Fortes
Hyperglycaemia is a primary cause of vascular complications in diabetes. A hallmark of these vascular complications is endothelial cell dysfunction, which is partly due to reduced production of nitric oxide. The aim of this study was to verify the influence of improved glycaemic control with chlorpropamide on microvascular reactivity, endothelial nitric oxide synthase (e-NOS) expression, and NOS activity in neonatal streptozotocin-induced diabetic rats (n-STZ). Diabetes was induced by STZ injection into neonates Wistar rats...
August 2007: Journal of Pharmacy and Pharmacology
Takashi Tsuchioka, Toshio Fujiwara, Masakatu Sunagawa
BACKGROUND: The objective of the present study was to ascertain whether simultaneous administration of glutamic acid (Glu) and taurine (Tau) to patients on total parenteral nutrition (TPN) could improve intestinal mucosal atrophy and suppress bacterial translocation. METHODS: A 5-day TPN study was conducted in 5-week-old Sprague-Dawley rats. Commercially available Glu was used for TPN in group G and was enhanced with Tau (500 mg kg(-1) day(-1)) in group GT. Oral nutrition was provided in group C controls...
September 2006: Journal of Pediatric Surgery
Vera Turchetti, Letizia Boschi, Giovanni Donati, Luca Trabalzini, Sandro Forconi
Previous studies showed that endothelial alterations caused by physical stress worsened the hemorheological parameters mainly in patients affected by ischemic vascular diseases: major vascular alterations have been found in patients with very high endothelial dysfunction indexes: these indexes are given by the various substances produced by the endothelium, but it is very difficult to have a value which clearly identifies the real state of the endothelial alteration. The function of the NO, an endogenous vasodilator whose synthesis is catalyzed by NOs, can be determined by the Citrulline/Arginine ratio, which represents the level of activity of the enzyme...
2006: Advances in Experimental Medicine and Biology
Guido Bellinghieri, Domenico Santoro, Agostino Mallamace, Rosa Maria Di Giorgio, Grazia De Luca, Vincenzo Savica
L-Arginine is an essential amino acid for infants and growing children, as well as for pregnant women. This amino acid is a substrate for at least 5 enzymes identified in mammals, including arginase, arginine-glycine transaminase, kyotorphine synthase, nitric oxide synthase, and arginine decarboxylase. L-arginine is essential for the synthesis of creatine, urea, polyamines, nitric oxide, and agmatine. Arginine may be considered an essential amino acid in sepsis, and its supplementation could be beneficial in this clinical setting by improving microcirculation and protein anabolism...
July 2006: Journal of Renal Nutrition
Eliana H Akamine, Elisa M Kawamoto, Cristoforo Scavone, Dorothy Nigro, Maria Helena C Carvalho, Rita de Cássia A Tostes, Luiz R G Britto, Zuleica B Fortes
Diabetes-induced vascular dysfunction has mainly been studied in males. However, the mechanisms involved may not correspond to those in females. Here we analyzed the effects of tetrahydrobiopterin (BH(4)) and chronic insulin on the physiology of mesenteric arterioles of alloxan-diabetic female rats. The parameters studied were the mesenteric arteriolar reactivity (intravital microscopy), nitric oxide synthase (NOS) activity (conversion of L-arginine to L-citrulline), eNOS gene expression (RT-PCR), NO production (diaminofluorescein), reactive oxygen species (ROS) generation (intravital fluorescence microscopy) and Cu/Zn superoxide dismutase (SOD) activity (spectrophotometry) and gene expression (RT-PCR)...
2006: Journal of Vascular Research
Richard Kradin, Osamu Matsubara, Eugene J Mark
Pulmonary capillary hemangiomatosis (PCH) is an unusual disorder characterized by the proliferation of capillaries in the alveolar septa and pulmonary interstitium. Originally conceived as a primary idiopathic disorder of the pulmonary microcirculation, recent studies have demonstrated that PCH may be associated with other pathologies. Nitric oxide (NO) is a gaseous free radical with protean biological effects that is released during the intracellular conversion of arginine to citrulline. Nitric oxide synthases (NOS) mediate the production of NO and the release of NO in the microvasculature is specifically catalyzed by endothelial NOS (NOS-III)...
December 2005: Experimental and Molecular Pathology
Yvette C Luiking, Martijn Poeze, Graham Ramsay, Nicolaas E P Deutz
Sepsis is a systemic response to an infection, with high morbidity and mortality rates. Metabolic changes during infection and sepsis could be related to changes in metabolism of the amino acid L-arginine. In sepsis, protein breakdown is increased, which is a key process to maintain arginine delivery because both endogenous de novo arginine production from citrulline and food intake are reduced. Arginine catabolism, on the other hand, is markedly increased by enhanced use of arginine via the arginase and nitric oxide pathways...
January 2005: JPEN. Journal of Parenteral and Enteral Nutrition
Yvette C Luiking, Martijn Poeze, Cornelis H Dejong, Graham Ramsay, Nicolaas E Deutz
OBJECTIVE: Sepsis is a major health problem considering its significant morbidity and mortality rate. The amino acid L-arginine has recently received substantial attention in relation to human sepsis. However, knowledge of arginine metabolism during sepsis is limited. Therefore, we reviewed the current knowledge about arginine metabolism in sepsis. DATA SOURCE: This review summarizes the literature on arginine metabolism both in general and in relation to sepsis...
October 2004: Critical Care Medicine
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