ArticleProceedings of the National Academy of Sciences of the United States of America2013
Arginase regulates red blood cell nitric oxide synthase and export of cardioprotective nitric oxide bioactivity.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 75 papers.
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Who cites it
75 citing papers in PubMed, 143 citations in OpenAlex.
- Hypoxic erythrocytes mediate cardioprotection through activation of soluble guanylate cyclase and release of cyclic GMP.The Journal of clinical investigation · 2023Trial
- Effects of inorganic nitrate on ischaemia-reperfusion injury after coronary artery bypass surgery: a randomised controlled trial.British journal of anaesthesia · 2021Trial
- Loss of erythrocyte arginase-1 impairs vasorelaxation due to endothelial GSNOR overexpression and denitrosylation of G protein subunits.Redox biology · 2026Article
- The Ugly Side of NO: Erythrocyte-Derived NO and Atherosclerosis.Circulation research · 2026Article
- microRNA-210 in red blood cells differentially regulates vascular endothelial function between type 1 and type 2 diabetes.Physiological reports · 2026Article
- Red Blood Cells in Normal and Pathological States: Redox Reactions of Hemoglobin.Molecules (Basel, Switzerland) · 2026Review
- The Janus face of L-arginine supplementation in cardiovascular health and aging exploration of underlying mechanisms.Frontiers in aging · 2026Review
- Targeting Arginase 1 but Not Arginase 2 Protects from Myocardial Ischemia-Reperfusion Injury via Nitric Oxide Signaling by Red Blood Cells in Type 2 Diabetes.Antioxidants (Basel, Switzerland) · 2026Article
- Erythrocyte-derived extracellular vesicles induce endothelial dysfunction through arginase-1 and oxidative stress in type 2 diabetes.The Journal of clinical investigation · 2025Article
- RBC-GEM: A genome-scale metabolic model for systems biology of the human red blood cell.PLoS computational biology · 2025Article
- Article
- Biochemistry, pharmacology, and in vivo function of arginases.Pharmacological reviews · 2025Review
- Differences in endothelial function between patients with Type 1 and Type 2 diabetes: effects of red blood cells and arginase.Clinical science (London, England : 1979) · 2024Article
- Gasotransmitters and noble gases in cardioprotection: unraveling molecular pathways for future therapeutic strategies.Basic research in cardiology · 2024Review
- L-Arginine-Dependent Nitric Oxide Production in the Blood of Patients with Type 2 Diabetes: A Pilot, Five-Year Prospective Study.Life (Basel, Switzerland) · 2024Article
- NO-ferroheme is a signaling entity in the vasculature.Nature chemical biology · 2023Article
- Stimulation of Erythrocyte Soluble Guanylyl Cyclase Induces cGMP Export and Cardioprotection in Type 2 Diabetes.JACC. Basic to translational science · 2023Article
- The red blood cell as a mediator of endothelial dysfunction in patients with familial hypercholesterolemia and dyslipidemia.Journal of internal medicine · 2023Article
- A High-Throughput Colorimetric Microplate Assay for Determination of Plasma Arginase Activity.Methods in molecular biology (Clifton, N.J.) · 2023Article
- Association of Red Blood Cell Life Span with Abnormal Changes in Cardiac Structure and Function in Non-Dialysis Patients with Chronic Kidney Disease Stages 3-5.Journal of clinical medicine · 2022Article
15 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The theory that red blood cells (RBCs) generate and release nitric oxide (NO)-like bioactivity has gained considerable interest. However, it remains unclear whether it can be produced by endothelial NO synthase (eNOS), which is present in RBCs, and whether NO can escape scavenging by hemoglobin. The aim of this study was to test the hypothesis that arginase reciprocally controls NO formation in RBCs by competition with eNOS for their common substrate arginine and that RBC-derived NO is functionally active following arginase blockade. We show that rodent and human RBCs contain functional arginase 1 and that pharmacological inhibition of arginase increases export of eNOS-derived nitrogen oxides from RBCs under basal conditions. The functional importance was tested in an ex vivo model of myocardial ischemia-reperfusion injury. Inhibitors of arginase significantly improved postischemic functional recovery in rat hearts if administered in whole blood or with RBCs in plasma. By contrast, arginase inhibition did not improve postischemic recovery when administered with buffer solution or plasma alone. The protective effect of arginase inhibition was lost in the presence of a NOS inhibitor. Moreover, hearts from eNOS(-/-) mice were protected when the arginase inhibitor was given with blood from wild-type donors. In contrast, when hearts from wild-type mice were given blood from eNOS(-/-) mice, the arginase inhibitor failed to protect against ischemia-reperfusion. These results strongly support the notion that RBCs contain functional eNOS and release NO-like bioactivity. This process is under tight control by arginase 1 and is of functional importance during ischemia-reperfusion.
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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.