Cited by 577Nitric Oxide and Endothelin EffectsAmino Acid Enzymes and MetabolismPolyamine Metabolism and Applications

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ARGINASE: A CRITICAL REGULATOR OF NITRIC OXIDE SYNTHESIS AND VASCULAR FUNCTION

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Durante, William, Johnson, Fruzsina K, Johnson, Robert A·2007·Clinical and Experimental Pharmacology and Physiology

DOI 10.1111/j.1440-1681.2007.04638.xPMC PMC1955221

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Abstract

SUMMARY: Arginase is the focal enzyme of the urea cycle hydrolysing l‐arginine to urea and l‐ornithine. Emerging studies have identified arginase in the vasculature and have implicated this enzyme in the regulation of nitric oxide (NO) synthesis and the development of vascular disease. Arginase inhibits the production of NO via several potential mechanisms, including competition with NO synthase (NOS) for the substrate l‐arginine, uncoupling of NOS resulting in the generation of the NO scavenger, superoxide and peroxynitrite, repression of the translation and stability of inducible NOS protein, inhibition of inducible NOS activity via the generation of urea and by sensitization of NOS to its endogenous inhibitor asymmetric dimethyl‐l‐arginine. Upregulation of arginase inhibits endothelial NOS‐mediated NO synthesis and may contribute to endothelial dysfunction in hypertension, ageing, ischaemia–reperfusion and diabetes. Arginase also redirects the metabolism of l‐arginine to l‐ornithine and the formation of polyamines and l‐proline, which are essential for smooth muscle cell growth and collagen synthesis. Therefore, the induction of arginase may also promote aberrant vessel wall remodelling and neointima formation. Arginase represents a promising novel therapeutic target that may reverse endothelial and smooth muscle cell dysfunction and prevent vascular disease.

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Vascular endothelial cells synthesize nitric oxide from L-arginine
Palmer, R. M. J., Ashton, D., & Moncada, S. (1988) · Nature · doi:10.1038/333664a0 · Cited by 4,786
POLYAMINES
Tabor, C. W., & Tabor, H. (1984) · Annual Review of Biochemistry · doi:10.1146/annurev.bi.53.070184.003533 · Cited by 3,111
Arginine metabolism: nitric oxide and beyond
WU, G., & MORRIS, S. M. (1998) · Biochemical Journal · doi:10.1042/bj3360001 · Cited by 2,811
Correction of endothelial dysfunction in coronary microcirculation of hypercholesterolaemic patients by L-arginine
Drexler, H., Zeiher, A. M., Meinzer, K., & Just, H. (1991) · The Lancet · doi:10.1016/0140-6736(91)92372-9 · Cited by 794
Dysregulated Arginine Metabolism, Hemolysis-Associated Pulmonary Hypertension, and Mortality in Sickle Cell Disease
Morris, C. R. (2005) · JAMA · doi:10.1001/jama.294.1.81 · Cited by 769
Antiatherogenic effects of L-arginine in the hypercholesterolemic rabbit.
Cooke, J. P., Singer, A. H., Tsao, P. S., Zera, P. H., Rowan, R. A., & Billingham, M. E. (1992) · Journal of Clinical Investigation · doi:10.1172/jci115937 · Cited by 683
Nitric oxide and its role in the cardiovascular system
Loscalzo, J., & Welch, G. N. (1995) · Progress in Cardiovascular Diseases · doi:10.1016/s0033-0620(05)80001-5 · Cited by 613
Comparative properties of arginases
Jenkinson, C. P., Grody, W. W., & Cederbaum, S. D. (1996) · Comparative Biochemistry and Physiology Part B Biochemistry and Molecular Biology · doi:10.1016/0305-0491(95)02138-8 · Cited by 610
Nitrogen metabolism and ornithine cycle function
Meijer, A. J., Lamers, W. H., & Chamuleau, R. A. F. M. (1990) · Physiological Reviews · doi:10.1152/physrev.1990.70.3.701 · Cited by 570
Arginine: Biochemistry, Physiology, and Therapeutic Implications
Barbul, A. (1986) · Journal of Parenteral and Enteral Nutrition · doi:10.1177/0148607186010002227 · Cited by 531

Show all 75 references

Research works printed but not linked: 1

Durante W, 2005, Arginase induces endothelial dysfunction and hypertension in obese Zucker rats, Diabetes, 54, A51

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“Similarly, promoting abnormal remodeling and neointimal hyperplasia reduced NO bioavailability [134, 135].”
Background
Insights into the arginine paradox: evidence against the importance of subcellular location of arginase and eNOS
Elms, S. C., Chen, F., Wang, Y., Qian, J., Askari, B., Yu, Y., Pandey, D., Iddings, J. A., Caldwell, R. B., & Fulton, D. J. (2013) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00755.2012 · Cited by 83
“The importance of arginase to this relationship is underscored by a large number of studies showing that arginase expression and activity are increased in many cardiovascular disease states, such as atherosclerosis and diabetes, and that this occurs contemporaneously with reduced NO levels (2, 11, 32, 46, 53, 56, 57).”
BackgroundInfluential
Hypoxic upregulation of arginase II in human lung endothelial cells
Krotova, K. Y., Patel, J. M., Block, E. R., & Zharikov, S. I. (2010) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00068.2010 · Cited by 81
“It has been shown that arginase is responsible for reduced NO levels in many pathological conditions (10, 16, 28, 29, 52, 53).”
Background
Endothelial dysfunction and vascular disease in later life
Virdis, A., Ghiadoni, L., Giannarelli, C., & Taddei, S. (2010) · Maturitas · doi:10.1016/j.maturitas.2010.04.006 · Cited by 79
Bench to bedside review: therapeutic modulation of nitric oxide in sepsis—an update
Lambden, S. (2019) · Intensive Care Medicine Experimental · doi:10.1186/s40635-019-0274-x · Cited by 82
Arginase inhibition restores in vivo coronary microvascular function in type 2 diabetic rats
Grönros, J., Jung, C., Lundberg, J. O., Cerrato, R., Östenson, C., & Pernow, J. (2011) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00560.2010 · Cited by 76
Gr1intCD11b+ Myeloid-Derived Suppressor Cells in Mycobacterium tuberculosis Infection
Obregón-Henao, A., Henao-Tamayo, M., Orme, I. M., & Ordway, D. J. (2013) · PLoS ONE · doi:10.1371/journal.pone.0080669 · Cited by 74
“It would be interesting to evaluate if arginase has a causal role in lung necrosis, by indirectly affecting endothelial function in blood vessels in close proximity to granulomas [52].”
Background
Oral atorvastatin therapy restores cutaneous microvascular function by decreasing arginase activity in hypercholesterolaemic humans
Holowatz, L. A., Santhanam, L., Webb, A. K., Berkowitz, D. E., & Kenney, W. L. (2011) · The Journal of Physiology · doi:10.1113/jphysiol.2010.203935 · Cited by 77
“Functionally, we could not determine the specific arginase isoform mediating the reduction in NO bioavailability due to the lack of isoform specific inhibitors (Cederbaum et al. 2004; Durante et al. 2007).”
Background
Nitric oxide in the regulation of the sleep-wake states
Cespuglio, R., Amrouni, D., Meiller, A., Buguet, A., & Gautier-Sauvigné, S. (2012) · Sleep Medicine Reviews · doi:10.1016/j.smrv.2012.01.006 · Cited by 75
Acute l-arginine supplementation increases muscle blood volume but not strength performance
Álvares, T. S., Conte, C. A., Paschoalin, V. M. F., Silva, J. T., Meirelles, C. D. M., Bhambhani, Y. N., & Gomes, P. S. C. (2012) · Applied Physiology, Nutrition, and Metabolism · doi:10.1139/h11-144 · Cited by 71
NOX2-Induced Activation of Arginase and Diabetes-Induced Retinal Endothelial Cell Senescence
Rojas, M., Lemtalsi, T., Toque, H. A., Xu, Z., Fulton, D. J., Caldwell, R. W., & Caldwell, R. B. (2017) · Antioxidants · doi:10.3390/antiox6020043 · Cited by 73
“Arginase activity was assayed by measuring urea production from L-arginine as previously described [31].”
Background
Relaxin improves TNF-α-induced endothelial dysfunction: the role of glucocorticoid receptor and phosphatidylinositol 3-kinase signalling
Dschietzig, T. B., Brecht, A., Bartsch, C., Baumann, G., Stangl, K., & Alexiou, K. (2012) · Cardiovascular Research · doi:10.1093/cvr/cvs149 · Cited by 74
“The prevailing scientific opinion is that the enzyme starves eNOS from L-arginine, which then results in uncoupling, superoxide production, peroxynitrite rise, and oxidative damage to the catalytic centre of eNOS.(41)”
Background
Immunohistochemical study of arginase 1 and 2 in various tissues of rats
Choi, S., Park, C., Ahn, M., Lee, J. H., & Shin, T. (2011) · Acta Histochemica · doi:10.1016/j.acthis.2011.09.002 · Cited by 70
Arginase 2 promotes neurovascular degeneration during ischemia/reperfusion injury
Shosha, E., Xu, Z., Yokota, H., SAUL, A. B., Rojas, M., Caldwell, R. W., Caldwell, R. B., & Narayanan, S. P. (2016) · Cell Death and Disease · doi:10.1038/cddis.2016.295 · Cited by 68
Asymmetric dimethylarginine (ADMA) elevation and arginase up‐regulation contribute to endothelial dysfunction related to insulin resistance in rats and morbidly obese humans
Assar, M. E., Angulo, J., Santos‐Ruiz, M., de Adana, J. C. R., Martínez, M. L. P., Sánchez‐Ferrer, A., Hernández, A., & Rodríguez‐Mañas, L. (2016) · The Journal of Physiology · doi:10.1113/jp271836 · Cited by 69
Pulmonary hypertension in thalassemia
Morris, C. R., & Vichinsky, E. P. (2010) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2010.05580.x · Cited by 69
Local Arginase Inhibition during Early Reperfusion Mediates Cardioprotection via Increased Nitric Oxide Production
Gonon, A. T., Jung, C., Katz, A., Westerblad, H., Shemyakin, A. S., Sjöquist, P.-O. B., Lundberg, J. O., & Pernow, J. (2012) · PLoS ONE · doi:10.1371/journal.pone.0042038 · Cited by 68
“Arginase I is a cytosolic enzyme expressed primarily in the liver but also in vascular smooth muscle, endothelial cells and the myocardium [12,13].”
Background
Arginase Inhibition Improves Microvascular Endothelial Function in Patients With Type 2 Diabetes Mellitus
Kövamees, O., Shemyakin, A. S., Checa, A., Wheelock, C. E., Lundberg, J. O., Östenson, C., & Pernow, J. (2016) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2016-2007 · Cited by 70
L-Arginine-Nitric Oxide-Asymmetric Dimethylarginine Pathway and the Coronary Circulation: Translation of Basic Science Results to Clinical Practice
Cziráki, A., Lenkey, Z., Sulyok, E., Szokodi, I., & Koller, Á. (2020) · Frontiers in Pharmacology · doi:10.3389/fphar.2020.569914 · Cited by 72
Increased arginase levels in heart failure represent a therapeutic target to rescue microvascular perfusion
Quitter, F., Figulla, H. R., Ferrari, M. W., Pernow, J., & Jung, C. (2013) · Clinical Hemorheology and Microcirculation · doi:10.3233/ch-2012-1617 · Cited by 70
“Both isoforms of arginase are expressed in the cardiovascular system [15].”
Arginase Activity Mediates Retinal Inflammation in Endotoxin-Induced Uveitis
Zhang, W., Baban, B., Rojas, M., Tofigh, S., Virmani, S. K., Patel, C., Behzadian, M. A., Romero, M. J., Caldwell, R. W., & Caldwell, R. B. (2009) · American Journal Of Pathology · doi:10.2353/ajpath.2009.081115 · Cited by 70
“The American Journal of Pathology, Vol. 175, No. 2, August 2009 Copyright © American Society for Investigative Pathology DOI: 10.2353/ajpath.2009.081115 891 vascular endothelial cells, smooth muscle cells, and macrophages.21–23 Given that L-arginine is also an indispensible substrate for nitric oxide synthase (NOS) in…”
BackgroundInfluential
Neuroprotective modulation of microglia effector functions following priming with interleukin 4 and 13: current limitations in understanding their mode-of-action
Quarta, A., Berneman, Z. N., & Ponsaerts, P. (2020) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2020.03.023 · Cited by 68
Mechanisms and clinical implications of endothelium-dependent vasomotor dysfunction in coronary microvasculature
Sabe, S. A., Feng, J., Sellke, F. W., & Abid, M. R. (2022) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00603.2021 · Cited by 67
Increase in Red Blood Cell-Nitric Oxide Synthase Dependent Nitric Oxide Production during Red Blood Cell Aging in Health and Disease: A Study on Age Dependent Changes of Rheologic and Enzymatic Properties in Red Blood Cells
Bizjak, D. A., Brinkmann, C. K., Bloch, W., & Grau, M. (2015) · PLoS ONE · doi:10.1371/journal.pone.0125206 · Cited by 67
“Different cardiovascular disease states are described which exhibit decreased NO availability and increased arginase activity such as hypertension and diabetes [47,79–81].”
Background
Regulation of smooth muscle by inducible nitric oxide synthase and NADPH oxidase in vascular proliferative diseases
Ginnan, R. G., Guikema, B. J., Halligan, K. E., Singer, H. A., & Jourd’heuil, D. (2008) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2007.12.025 · Cited by 67
Ascorbic acid or l -arginine improves cutaneous microvascular function in chronic kidney disease
DuPont, J. J., Farquhar, W. B., Townsend, R. R., & Edwards, D. G. (2011) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00419.2011 · Cited by 65
“The two known isoforms of arginase (arginase I and arginase II) exist in the vasculature and have been implicated in endothelial dysfunction (9).”
Background
Arginase II Deletion Increases Corpora Cavernosa Relaxation in Diabetic Mice
Toque, H. A., Tostes, R. C., Yao, L., Xu, Z., Webb, R. C., Caldwell, R. B., & Caldwell, R. W. (2010) · The Journal of Sexual Medicine · doi:10.1111/j.1743-6109.2010.02098.x · Cited by 65
“Previous studies in our lab and others indicate that diabetes elevates vascular Arg activity, which contributes to endothelial dysfunction [11,12,13].”
Arginase as a mediator of diabetic retinopathy
Patel, C. (2013) · Frontiers in Immunology · doi:10.3389/fimmu.2013.00173 · Cited by 64
Inflammatory monocytes are detrimental to the host immune response during acute infection with Cryptococcus neoformans
Heung, L. J., & Hohl, T. M. (2019) · PLoS Pathogens · doi:10.1371/journal.ppat.1007627 · Cited by 64
Development and validation of GC–MS methods for the comprehensive analysis of amino acids in plasma and urine and applications to the HELLP syndrome and pediatric kidney transplantation: evidence of altered methylation, transamidination, and arginase activity
Hanff, E., Ruben, S., Kreuzer, M., Bollenbach, A., Kayacelebi, A. A., Das, A. M., von Versen‐Höynck, F., von Kaisenberg, C., Haffner, D., Ückert, S., et al. (2019) · Amino Acids · doi:10.1007/s00726-018-02688-w · Cited by 63
The ageing endothelium, cardiovascular risk and disease in man
Versari, D., Daghini, E., Virdis, A., Ghiadoni, L., & Taddei, S. (2008) · Experimental Physiology · doi:10.1113/expphysiol.2008.043356 · Cited by 62
Effect of stroke on arginase expression and localization in the rat brain
Quirié, A., Demougeot, C., Bertrand, N., Mossiat, C. M., Garnier, P. E., Marie, C., & Prigent‐Tessier, A. (2013) · European Journal of Neuroscience · doi:10.1111/ejn.12111 · Cited by 62
“…to be involved in the decreased production of NO observed in different pathologies associated with low- or high-grade inflammation (Lee et al., 2003; Demougeot et al., 2005; Topal et al., 2006; Durante et al., 2007; Khallou-Laschet et al., 2010; Lewis et al., 2010; Benson et al., 2011).”
Background
Nitric Oxide Releasing Coronary Stent: A New Approach Using Layer-by-Layer Coating and Liposomal Encapsulation
Elnaggar, M. A., Seo, S. H., Gobaa, S., Lim, K. S., Bae, I., Jeong, M. H., Han, D. K., & Joung, Y. K. (2016) · Small · doi:10.1002/smll.201600337 · Cited by 64
Mechanisms of sepsis-induced acute liver injury: a comprehensive review
Guo, Y., Guo, W., Chen, H., Sun, J., & Yin, Y. (2025) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2025.1504223 · Cited by 73
“In studies related to liver diseases, ARG1 can regulate nitric oxide levels and vascular function (Durante et al., 2007), modulate immune responses, and promote tissue repair (Wynn and Ramalingam, 2012).”
Hypoxia-reduced nitric oxide synthase activity is partially explained by higher arginase-2 activity and cellular redistribution in human umbilical vein endothelium
Prieto, C. P., Krause, B. J., Quezada, C., Martín, R. S., Sobrevía, L., & Casanello, P. C. (2011) · Placenta · doi:10.1016/j.placenta.2011.09.003 · Cited by 61
“Despite that arginase-2 has been classically described as a mitochondrial enzyme [9,11], several studies have shown the presence of a functional arginase-2 outside themitochondria [16,20,33,34].”
Background
Macrophage heterogeneity and energy metabolism
Verdeguer, F., & Aouadi, M. (2017) · Experimental Cell Research · doi:10.1016/j.yexcr.2017.03.043 · Cited by 58
Effect of Arginase Inhibition on Ischemia-Reperfusion Injury in Patients with Coronary Artery Disease with and without Diabetes Mellitus
Kövamees, O., Shemyakin, A., & Pernow, J. (2014) · PLoS ONE · doi:10.1371/journal.pone.0103260 · Cited by 57
“Endothelium-dependent vasodilatation was assessed by flow-mediated dilatation (FMD) of the radial artery before and after 20 min ischemia-reperfusion during intra-arterial infusion of the arginase inhibitor (Nv-hydroxy-norL-arginine, 0.1 mg/min) or saline.”
BackgroundInfluential

Authors: Durante, W., Johnson, F. K., & Johnson, R. A.
Affiliations: University of Missouri (US)
Tulane University (US)
Corresponding author: Durante, William
ORCID: Durante, William
Johnson, Robert A
Venue: Clinical and Experimental Pharmacology and Physiology
Publisher: Wiley
Published: 2007-04-26
Volume: 34
Issue: 9
Pages: 906-911
ISSN: 0305-1870 (ISSN-L)
1440-1681
DOI: 10.1111/j.1440-1681.2007.04638.x
PMC: PMC1955221
OpenAlex: W2125031388
Cited by: 577
References: 75
Citations by year: 2026: 25 · 2025: 29 · 2024: 21 · 2023: 27 · 2022: 32 · 2021: 45 · 2020: 33 · 2019: 21 · 2018: 25 · 2017: 23 · 2016: 33 · 2015: 25 · 2014: 45 · 2013: 40 · 2012: 29
FWCI: 2.88
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations: Clinical and Experimental Pharmacology and Physiology (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Funders: National Heart, Lung, and Blood Institute (R01HL074966, R01HL076187, R01HL059976)
National Center for Research Resources (P20RR017659)
Topics: Health Sciences › Medicine › Physiology (medical) › Nitric Oxide and Endothelin Effects
Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Amino Acid Enzymes and Metabolism
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Polyamine Metabolism and Applications
Keywords: arginase, nitric oxide production, nitric oxide synthase, arginine metabolism, urea cycle, endothelial dysfunction, vascular disease, asymmetric dimethylarginine, inducible nitric oxide synthase, superoxide, peroxynitrite, polyamines, proline, smooth muscle cell proliferation, neointima formation, hypertension, ischaemia-reperfusion, diabetes mellitus, aging
MeSH terms: Animals, Arginase, Arginine, Cardiovascular Diseases, Collagen, Endothelium, Vascular, Homeostasis, Humans, Muscle, Smooth, Vascular, Nitric Oxide, Urea, Reactive Oxygen Species, Cell Proliferation, Nitric Oxide Synthase Type III

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ARGINASE: A CRITICAL REGULATOR OF NITRIC OXIDE SYNTHESIS AND VASCULAR FUNCTION

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