ArticleCirculation2021
Red Blood Cell and Endothelial eNOS Independently Regulate Circulating Nitric Oxide Metabolites and Blood Pressure.
Article in Circulation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 112 papers, 1 of them a synthesis that pooled it.
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Who cites it
112 citing papers in PubMed, 1 synthesis or guideline pooled it, 193 citations in OpenAlex.
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- Metabolic reprogramming in diabetic panvascular disease: Molecular mechanism and therapeutic strategies.iScience · 2026Review
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- Preclinical Evaluation of Berry Extracts as a Nutritional Intervention to Alleviate Myocardial Ischemia-Reperfusion Injury and Atherosclerosis Development.Phytotherapy research : PTR · 2026Article
- Curcumin's Protective Effects Against HMolecules (Basel, Switzerland) · 2026Review
- Hypoxia-injured pulmonary vascular targeting and microenvironment-responsive nanoparticle to treat hypoxic pulmonary hypertension.Journal of nanobiotechnology · 2026Article
- 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
- Endothelial Nitric Oxide Synthase Restores Diabetic Dentin Regeneration via AKT/Endothelial Nitric Oxide Synthase Axis.International dental journal · 2026Article
- SIRPα extracellular domain shed from neutrophils by ADAM10 aggravates sepsis via initiating nitric oxide release from erythrocyte.Journal of advanced research · 2026Article
- Sensitive and specific methodology for detection of labile NO-ferroheme complexes in vitro and in blood.Redox biology · 2026Article
- Direct pharmacological targeting of Piezo1 by Paeoniflorin: a novel therapeutic approach for renal fibrosis.Journal of advanced research · 2026Article
- Liposomal encapsulation of L-arginine and L-citrulline enhances pharmacokinetics and therapeutic effects in a model of preeclampsia and fetal growth restriction.Scientific reports · 2026Article
- The lung-brain axis: elucidating the mechanisms of pulmonary-driven neurological disorders.Journal of neuroinflammation · 2026Review
- Effect of L-Citrulline Intake on Blood Pressure in Cold Environments: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.Food science & nutrition · 2026Review
- Red Blood Cells Internalize Extracellular DNA via Apoptotic Bodies with Clinical Relevance to Cancer Patients.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Article
52 more citing papers are in PubMed but not listed here.
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Authors and funding
22 authors at 7 institutions in 7 countries.
Funding
Abstract
backgroundCurrent paradigms suggest that nitric oxide (NO) produced by endothelial cells (ECs) through endothelial nitric oxide synthase (eNOS) in the vessel wall is the primary regulator of blood flow and blood pressure. However, red blood cells (RBCs) also carry a catalytically active eNOS, but its role is controversial and remains undefined. This study aimed to elucidate the functional significance of RBC eNOS compared with EC eNOS for vascular hemodynamics and nitric oxide metabolism.
methodsWe generated tissue-specific loss- and gain-of-function models for eNOS by using cell-specific Cre-induced gene inactivation or reactivation. We created 2 founder lines carrying a floxed eNOS (eNOS
resultsThe EC eNOS KOs exhibited significantly impaired aortic dilatory responses to acetylcholine, loss of flow-mediated dilation, and increased systolic and diastolic blood pressure. RBC eNOS KO mice showed no alterations in acetylcholine-mediated dilation or flow-mediated dilation but were hypertensive. Treatment with the nitric oxide synthase inhibitor
conclusionsThese data reveal that eNOS in ECs and RBCs contribute independently to blood pressure homeostasis.
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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.