ArticleAmerican journal of physiology. Heart and circulatory physiology2013
Insights into the arginine paradox: evidence against the importance of subcellular location of arginase and eNOS.
Article in American journal of physiology. Heart and circulatory physiology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
36 citing papers in PubMed, 78 citations in OpenAlex.
- Guanidines: Privileged Scaffolds Against Neglected Tropical Diseases: A Review.Pharmaceuticals (Basel, Switzerland) · 2026Review
- The rise of astrocytes: are they guardians or troublemakers of the brain disorder?Experimental & molecular medicine · 2026Review
- The Janus face of L-arginine supplementation in cardiovascular health and aging exploration of underlying mechanisms.Frontiers in aging · 2026Review
- The Physiological Roles and Pathological Implications of Urea Transporters in the Cardiovascular System.Biomedicines · 2025Review
- L-Arginine and Nitric Oxide in Vascular Regulation-Experimental Findings in the Context of Blood Donation.Nutrients · 2025Review
- Metabolic Regulation in Acute Respiratory Distress Syndrome: Implications for Inflammation and Oxidative Stress.International journal of chronic obstructive pulmonary disease · 2025Review
- Biochemistry, pharmacology, and in vivo function of arginases.Pharmacological reviews · 2025Review
- Subcellular Localization Guides eNOS Function.International journal of molecular sciences · 2024Review
- Arginine Supplementation in MELAS Syndrome: What Do We Know about the Mechanisms?International journal of molecular sciences · 2024Review
- Endothelial Dysfunction in Obesity and Therapeutic Targets.Advances in experimental medicine and biology · 2024Review
- A review of nitric oxide and oxidative stress in typical ovulatory women and in the pathogenesis of ovulatory dysfunction in PCOS.Reproductive biology and endocrinology : RB&E · 2023Review
- Albumin Is a Component of the Esterase Status of Human Blood Plasma.International journal of molecular sciences · 2023Article
- Regulated Arginine Metabolism in Immunopathogenesis of a Wide Range of Diseases: Is There a Way to Pass between Scylla and Charybdis?Current issues in molecular biology · 2023Review
- Effect of electroacupuncture on haemodynamic changes during intubation for general anaesthesia is mediated by nitric oxide synthase‑3 via the regulation of microRNA‑155, microRNA‑335 and microRNA‑383.Molecular medicine reports · 2023Article
- Targeting Arginine in COVID-19-Induced Immunopathology and Vasculopathy.Metabolites · 2022Review
- Protective role of Cav-1 in pneumolysin-induced endothelial barrier dysfunction.Frontiers in immunology · 2022Article
- Microcirculatory Function during Endotoxemia-A Functional Citrulline-Arginine-NO Pathway and NOS3 Complex Is Essential to Maintain the Microcirculation.International journal of molecular sciences · 2021Article
- Interplay Between Reactive Oxygen/Reactive Nitrogen Species and Metabolism in Vascular Biology and Disease.Antioxidants & redox signaling · 2021Review
- L-Arginine Reduces Nitro-Oxidative Stress in Cultured Cells with Mitochondrial Deficiency.Nutrients · 2021Article
- Is the Arginase Pathway a Novel Therapeutic Avenue for Diabetic Retinopathy?Journal of clinical medicine · 2020Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
Reduced production of nitric oxide (NO) is one of the first indications of endothelial dysfunction and precedes overt cardiovascular disease. Increased expression of Arginase has been proposed as a mechanism to account for diminished NO production. Arginases consume l-arginine, the substrate for endothelial nitric oxide synthase (eNOS), and l-arginine depletion is thought to competitively reduce eNOS-derived NO. However, this simple relationship is complicated by the paradox that l-arginine concentrations in endothelial cells remain sufficiently high to support NO synthesis. One mechanism proposed to explain this is compartmentalization of intracellular l-arginine into distinct, poorly interchangeable pools. In the current study, we investigated this concept by targeting eNOS and Arginase to different intracellular locations within COS-7 cells and also BAEC. We found that supplemental l-arginine and l-citrulline dose-dependently increased NO production in a manner independent of the intracellular location of eNOS. Cytosolic arginase I and mitochondrial arginase II reduced eNOS activity equally regardless of where in the cell eNOS was expressed. Similarly, targeting arginase I to disparate regions of the cell did not differentially modify eNOS activity. Arginase-dependent suppression of eNOS activity was reversed by pharmacological inhibitors and absent in a catalytically inactive mutant. Arginase did not directly interact with eNOS, and the metabolic products of arginase or downstream enzymes did not contribute to eNOS inhibition. Cells expressing arginase had significantly lower levels of intracellular l-arginine and higher levels of ornithine. These results suggest that arginases inhibit eNOS activity by depletion of substrate and that the compartmentalization of l-arginine does not play a major role.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.