ArticleThe Journal of clinical investigation1999
The pulmonary circulation of homozygous or heterozygous eNOS-null mice is hyperresponsive to mild hypoxia.
Article in The Journal of clinical investigation, 1999. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 92 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
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Who cites it
92 citing papers in PubMed.
- Plasma glutamate-modulated interaction of A2AR and mGluR5 on BMDCs aggravates traumatic brain injury-induced acute lung injury.The Journal of experimental medicine · 2013Trial
- Mitochondrial arginase 2 regulates hematopoietic and cardiovascular adaptation to hypoxia.Blood vessels, thrombosis & hemostasis · 2026Article
- Hypoxia responses in arginase 2 deficient mice enhance cardiovascular health.bioRxiv : the preprint server for biology · 2025Article
- Pulmonary vascular remodeling in Fra-2 transgenic mice is driven by type 2 inflammation and accompanied by pulmonary vascular hyperresponsiveness.American journal of physiology. Lung cellular and molecular physiology · 2025Article
- Endothelial Nitric Oxide synthase (eNOS) in Preeclampsia: An Update.Journal of pregnancy and child health · 2024Article
- Association between hypoxic burden and common cardiometabolic diseases in patients with severe obstructive sleep apnea.Sleep & breathing = Schlaf & Atmung · 2023Article
- Sleep-Related Hypoxia, Right Ventricular Dysfunction, and Survival in Patients With Group 1 Pulmonary Arterial Hypertension.Journal of the American College of Cardiology · 2023Observational
- Metabolic reprogramming, oxidative stress, and pulmonary hypertension.Redox biology · 2023Review
- Vascular pathobiology of pulmonary hypertension.The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation · 2023Review
- Association between the Polymorphisms rs2070744, 4b/a and rs1799983 of theMedicina (Kaunas, Lithuania) · 2023Article
- PHD2 deletion in endothelial or arterial smooth muscle cells reveals vascular cell type-specific responses in pulmonary hypertension and fibrosis.Angiogenesis · 2022Article
- Type 2 diabetes progression differently affects endothelial function and vascular contractility in the aorta and the pulmonary artery.Scientific reports · 2021Article
- Pulmonary Hypertension in Acute and Chronic High Altitude Maladaptation Disorders.International journal of environmental research and public health · 2021Review
- Epigenetic Regulation of Pulmonary Arterial Hypertension-Induced Vascular and Right Ventricular Remodeling: New Opportunities?International journal of molecular sciences · 2020Review
- Mechanisms underlying selective coupling of endothelial CaThe Journal of physiology · 2020Article
- A novel cyclic biased agonist of the apelin receptor, MM07, is disease modifying in the rat monocrotaline model of pulmonary arterial hypertension.British journal of pharmacology · 2019Article
- Vascular Endothelial Growth Factor Receptor 3 Regulates Endothelial Function Through β-Arrestin 1.Circulation · 2019Article
- EXPRESS: Gremlin1 blocks vascular endothelial growth factor signalling in the pulmonary microvascular endothelium.Pulmonary circulation · 2018Article
- Things We "kNOw" and Do Not "kNOw" about Pulmonary Hypertension.American journal of respiratory and critical care medicine · 2018Article
- EETs promote hypoxic pulmonary vasoconstriction via constrictor prostanoids.American journal of physiology. Lung cellular and molecular physiology · 2017Article
32 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
12 authors.
Funding
Abstract
Acute hypoxic vasoconstriction and development of hypoxic pulmonary hypertension (PHTN) are unique properties of the pulmonary circulation. The pulmonary endothelium produces vasoactive factors, including nitric oxide (NO), that modify these phenomena. We tested the hypothesis that NO produced by endothelial nitric oxide synthase (eNOS) modulates pulmonary vascular responses to hypoxia using mice with targeted disruption of the eNOS gene (eNOS-/-). Marked PHTN was found in eNOS-/- mice raised in mild hypoxia when compared with either controls or eNOS-/- mice raised in conditions simulating sea level. We found an approximate twofold increase in partially and fully muscularized distal pulmonary arteries in eNOS-/- mice compared with controls. Consistent with vasoconstriction being the primary mechanism of PHTN, however, acute inhalation of 25 ppm NO resulted in normalization of RV pressure in eNOS-/- mice. In addition to studies of eNOS-/- mice, the dose-effect of eNOS was tested using heterozygous eNOS+/- mice. Although the lungs of eNOS+/- mice had 50% of normal eNOS protein, the response to hypoxia was indistinguishable from that of eNOS-/- mice. We conclude that eNOS-derived NO is an important modulator of the pulmonary vascular response to chronic hypoxia and that more than 50% of eNOS expression is required to maintain normal pulmonary vascular tone.
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