ArticleProceedings of the National Academy of Sciences of the United States of America2006
Arginase modulates myocardial contractility by a nitric oxide synthase 1-dependent mechanism.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 90 citations in OpenAlex.
- Article
- Pulmozyme Ameliorates LPS-Induced Lung Fibrosis but Provokes Residual Inflammation by Modulating Cell-Free DNA Composition and Controlling Neutrophil Phenotype.Biomolecules · 2025Article
- Biochemistry, pharmacology, and in vivo function of arginases.Pharmacological reviews · 2025Review
- Declining nitric oxide bioavailability in cardiovascular aging: mechanistic insights and emerging interventions.The journal of cardiovascular aging · 2025Article
- Calcium-Dependent Interaction of Nitric Oxide Synthase with CytochromeBrain sciences · 2023Article
- The Therapeutic Mechanism of Schisandrol A and Its Metabolites on Pulmonary Fibrosis Based on Plasma Metabonomics and Network Analysis.Drug design, development and therapy · 2023Article
- Arginase: shedding light on the mechanisms and opportunities in cardiovascular diseases.Cell death discovery · 2022Review
- Effects of arginase inhibition on myocardial CaPhysiological reports · 2022Article
- Article
- Semantic Multi-Classifier Systems Identify Predictive Processes in Heart Failure Models across Species.Biomolecules · 2018Article
- Arginase-II Deficiency Extends Lifespan in Mice.Frontiers in physiology · 2017Article
- Intravenous administration of piceatannol, an arginase inhibitor, improves endothelial dysfunction in aged mice.The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2017Article
- Arginase Inhibition Restores Peroxynitrite-Induced Endothelial Dysfunction via L-Arginine-Dependent Endothelial Nitric Oxide Synthase Phosphorylation.Yonsei medical journal · 2016Article
- Arginase Inhibition Reverses Endothelial Dysfunction, Pulmonary Hypertension, and Vascular Stiffness in Transgenic Sickle Cell Mice.Anesthesia and analgesia · 2016Article
- Nutrition Modulation of Cardiotoxicity and Anticancer Efficacy Related to Doxorubicin Chemotherapy by Glutamine and ω-3 Polyunsaturated Fatty Acids.JPEN. Journal of parenteral and enteral nutrition · 2016Article
- Effective suppression of nitric oxide production by HX106N through transcriptional control of heme oxygenase-1.Experimental biology and medicine (Maywood, N.J.) · 2015Article
- Nitric oxide synthases, S-nitrosylation and cardiovascular health: from molecular mechanisms to therapeutic opportunities (review).Molecular medicine reports · 2015Review
- Upregulation of arginase activity contributes to intracellular ROS production induced by high glucose in H9c2 cells.International journal of clinical and experimental pathology · 2015Article
- Arginase inhibition augments nitric oxide production and facilitates left ventricular systolic function in doxorubicin-induced cardiomyopathy in mice.Physiological reports · 2014Article
- Partial restoration of cardiac function with ΔPDZ nNOS in aged mdx model of Duchenne cardiomyopathy.Human molecular genetics · 2014Article
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Authors and funding
13 authors at 1 institution in 1 country.
Funding
Abstract
Cardiac myocytes contain two constitutive NO synthase (NOS) isoforms with distinct spatial locations, which allows for isoform-specific regulation. One regulatory mechanism for NOS is substrate (l-arginine) bioavailability. We tested the hypothesis that arginase (Arg), which metabolizes l-arginine, constrains NOS activity in the cardiac myocyte in an isoform-specific manner. Arg activity was detected in both rat heart homogenates and isolated myocytes. Although both Arg I and II mRNA and protein were present in whole heart, Arg II alone was found in isolated myocytes. Arg inhibition with S-(2-boronoethyl)-l-cysteine (BEC) augmented Ca(2+)-dependent NOS activity and NO production in myocytes, which did not depend on extracellular l-arginine. Arg II coimmunoprecipited with NOS1 but not NOS3. Isolation of myocyte mitochondrial fractions in combination with immuno-electron microscopy demonstrates that Arg II is confined primarily to the mitochondria. Because NOS1 positively modulates myocardial contractility, we determined whether Arg inhibition would increase basal myocardial contractility. Consistent with our hypothesis, Arg inhibition increased basal contractility in isolated myocytes by a NOS-dependent mechanism. Both the Arg inhibitors N-hydroxy-nor-l-arginine and BEC dose-dependently increased basal contractility in rat myocytes, which was inhibited by both nonspecific and NOS1-specific NOS inhibitors N(G)-nitro-l-arginine methyl ester and S-methyl-l-thiocitrulline, respectively. Also, BEC increased contractility in isolated myocytes from WT and NOS3 but not NOS1 knockout mice. We conclude that mitochondrial Arg II negatively regulates NOS1 activity, most likely by limiting substrate availability in its microdomain. These findings have implications for therapy in pathophysiologic states such as aging and heart failure in which myocardial NO signaling is disrupted.
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