ArticleProceedings of the National Academy of Sciences of the United States of America2007
Receptor-mediated activation of nitric oxide synthesis by arginine in endothelial cells.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 28 papers.
What it found
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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.
Characterization of the Metabolic Fate of an Oral L-arginine Form in Healthy Subjects Featuring Risk Factors Related to the Metabolic Syndrome.
Effect of Oral Supplementation With One Form of L-arginine on Vascular Endothelial Function in Healthy Subjects Featuring Risk Factors Related to the Metabolic Syndrome.
Who cites it
28 citing papers in PubMed, 83 citations in OpenAlex.
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- The Janus face of L-arginine supplementation in cardiovascular health and aging exploration of underlying mechanisms.Frontiers in aging · 2026Review
- Differential Sensitivity of Hippocampal GABAergic Neurons to Hypoxia and Ischemia-like Conditions Correlates with the Type of Calcium-Binding Protein Expressed.International journal of molecular sciences · 2025Article
- The Role of the Urea Cycle in the Alzheimer's Disease Brain.Journal of neurochemistry · 2025Review
- Vasoactive Biomarkers in Patients With Vasovagal Syncope During Head-Up Tilt Test: A Case-Control Study.Clinical Medicine Insights. Cardiology · 2022Article
- Effects of sex and estrous cycle on the brain and plasma arginine metabolic profile in rats.Amino acids · 2021Article
- A novel imidazolinone metformin-methylglyoxal metabolite promotes endothelial cell angiogenesis via the eNOS/HIF-1α pathway.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2021Article
- Symmetric Dimethylarginine is Altered in Patients After Myocardial Infarction and Predicts Adverse Outcomes.Journal of inflammation research · 2021Article
- Article
- CR6-interacting factor 1 deficiency reduces endothelial nitric oxide synthase activity by inhibiting biosynthesis of tetrahydrobiopterin.Scientific reports · 2020Article
- Agmatinase promotes the lung adenocarcinoma tumorigenesis by activating the NO-MAPKs-PI3K/Akt pathway.Cell death & disease · 2019Article
- Bidirectional Regulatory Effects of Dexmedetomidine on Porcine Coronary Tone In Vitro.Medical science monitor : international medical journal of experimental and clinical research · 2017Article
- Interactions of nitric oxide with α2 -adrenoceptors within the locus coeruleus underlie the facilitation of inhibitory avoidance memory by agmatine.British journal of pharmacology · 2016Article
- Dexmedetomidine inhibits vasoconstriction via activation of endothelial nitric oxide synthase.The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2016Article
- Agmatine induced NO dependent rat mesenteric artery relaxation and its impairment in salt-sensitive hypertension.Nitric oxide : biology and chemistry · 2013Article
- The unique role of dietary L-arginine in the acceleration of peritoneal macrophage sensitivity to bacterial endotoxin.Immunologic research · 2013Article
- Tetrahydrobiopterin, L-arginine and vitamin C act synergistically to decrease oxidant stress and increase nitric oxide that increases blood flow recovery after hindlimb ischemia in the rat.Molecular medicine (Cambridge, Mass.) · 2012Article
- Dexmedetomidine-induced contraction of isolated rat aorta is dependent on extracellular calcium concentration.Korean journal of anesthesiology · 2012Article
Corrections and comments
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Authors and funding
6 authors at 4 institutions in 2 countries.
Funding
Abstract
Arginine contains the guanidinium group and thus has structural similarity to ligands of imidazoline and alpha-2 adrenoceptors (alpha-2 AR). Therefore, we investigated the possibility that exogenous arginine may act as a ligand for these receptors in human umbilical vein endothelial cells and activate intracellular nitric oxide (NO) synthesis. Idazoxan, a mixed antagonist of imidazoline and alpha-2 adrenoceptors, partly inhibited L-arginine-initiated NO formation as measured by a Griess reaction. Rauwolscine, a highly specific antagonist of alpha-2 AR, at very low concentrations completely inhibited NO formation. Like L-arginine, agmatine (decarboxylated arginine) also activated NO synthesis, however, at much lower concentrations. We found that dexmedetomidine, a specific agonist of alpha-2 AR was very potent in activating cellular NO, thus indicating a possible role for alpha-2 AR in L-arginine-mediated NO synthesis. D-arginine also activated NO production and could be inhibited by imidazoline and alpha-2 AR antagonists, thus indicating nonsubstrate actions of arginine. Pertussis toxin, an inhibitor of G proteins, attenuated L-arginine-mediated NO synthesis, thus indicating mediation via G proteins. L-type Ca(2+) channel blocker nifedipine and phospholipase C inhibitor U73122 inhibited NO formation and thus implicated participation of a second messenger pathway. Finally, in isolated rat gracilis vessels, rauwolscine completely inhibited the L-arginine-initiated vessel relaxation. Taken together, these data provide evidence for binding of arginine to membrane receptor(s), leading to the activation of endothelial NO synthase (eNOS) NO production through a second messenger pathway. These findings provide a previously unrecognized mechanistic explanation for the beneficial effects of L-arginine in the cardiovascular system and thus provide new potential avenues for therapeutic development.
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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.