ArticleThe Journal of clinical investigation1998
Hypotension and reduced nitric oxide-elicited vasorelaxation in transgenic mice overexpressing endothelial nitric oxide synthase.
Article in The Journal of clinical investigation, 1998. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers, 2 of them syntheses that pooled it.
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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.
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Who cites it
68 citing papers in PubMed, 2 syntheses or guidelines pooled it, 280 citations in OpenAlex.
- Association between eNOS rs1799983 polymorphism and hypertension: a meta-analysis involving 14,185 cases and 13,407 controls.BMC cardiovascular disorders · 2021Pooled it
- An updated meta-analysis of endothelial nitric oxide synthase gene: three well-characterized polymorphisms with hypertension.PloS one · 2011Pooled it
- Lymphocyte-Specific Protein 1 Regulates Expression and Stability of Endothelial Nitric Oxide Synthase.Biomolecules · 2024Article
- Mechanisms of cytokine release syndrome and neurotoxicity of CAR T-cell therapy and associated prevention and management strategies.Journal of experimental & clinical cancer research : CR · 2021Review
- Oxidative Stress, GTPCH1, and Endothelial Nitric Oxide Synthase Uncoupling in Hypertension.Antioxidants & redox signaling · 2021Review
- Amelioration of Endothelial Dysfunction in Diabetes: Role of Takeda G Protein-Coupled Receptor 5.Frontiers in pharmacology · 2021Review
- Hematopoietic Cell-Expressed Endothelial Nitric Oxide Protects the Liver From Insulin Resistance.Arteriosclerosis, thrombosis, and vascular biology · 2020Article
- Macrophage, the potential key mediator in CAR-T related CRS.Experimental hematology & oncology · 2020Review
- Smooth muscle cytochrome b5 reductase 3 deficiency accelerates pulmonary hypertension development in sickle cell mice.Blood advances · 2019Article
- Elevated Neuropeptide Y in Endothelial Dysfunction Promotes Macrophage Infiltration and Smooth Muscle Foam Cell Formation.Frontiers in immunology · 2019Article
- Redox control of vascular smooth muscle cell function and plasticity.Laboratory investigation; a journal of technical methods and pathology · 2018Review
- CAR T cell-induced cytokine release syndrome is mediated by macrophages and abated by IL-1 blockade.Nature medicine · 2018Article
- Article
- Targeted overexpression of endothelial nitric oxide synthase in endothelial cells improves cerebrovascular reactivity in Ins2Akita-type-1 diabetic mice.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2016Article
- Article
- IL-33-Dependent Endothelial Activation Contributes to Apoptosis and Renal Injury in Orientia tsutsugamushi-Infected Mice.PLoS neglected tropical diseases · 2016Article
- Posttranscriptional and transcriptional regulation of endothelial nitric-oxide synthase during hypoxia: the role of microRNAs.Cellular & molecular biology letters · 2016Review
- Enhancing eNOS activity with simultaneous inhibition of IKKβ restores vascular function in Ins2(Akita+/-) type-1 diabetic mice.Laboratory investigation; a journal of technical methods and pathology · 2015Article
- Impact of eNOS-Dependent Oxidative Stress on Endothelial Function and Neointima Formation.Antioxidants & redox signaling · 2015Article
- M2 Macrophage Polarization Mediates Anti-inflammatory Effects of Endothelial Nitric Oxide Signaling.Diabetes · 2015Article
8 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Nitric oxide (NO), constitutively produced by endothelial nitric oxide synthase (eNOS), plays a major role in the regulation of blood pressure and vascular tone. We generated transgenic mice overexpressing bovine eNOS in the vascular wall using murine preproendothelin-1 promoter. In transgenic lineages with three to eight transgene copies, bovine eNOS-specific mRNA, protein expression in the particulate fractions, and calcium-dependent NOS activity were confirmed by RNase protection assay, immunoblotting, and L-arginine/citrulline conversion. Immunohistochemical studies revealed that eNOS protein was predominantly localized in the endothelial cells of aorta, heart, and lung. Blood pressure was significantly lower in eNOS-overexpressing mice than in control littermates. In the transgenic aorta, basal NO release (estimated by Nomega-nitro-L-arginine-induced facilitation of the contraction by prostaglandin F2alpha) and basal cGMP levels (measured by enzyme immunoassay) were significantly increased. In contrast, relaxations of transgenic aorta in response to acetylcholine and sodium nitroprusside were significantly attenuated, and the reduced vascular reactivity was associated with reduced response of cGMP elevation to these agents as compared with control aortas. Thus, our novel mouse model of chronic eNOS overexpression demonstrates that, in addition to the essential role of eNOS in blood pressure regulation, tonic NO release by eNOS in the endothelium induces the reduced vascular reactivity to NO-mediated vasodilators, providing several insights into the pathogenesis of nitrate tolerance.
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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.