ArticleVascular pharmacology2014
Intermittent hypoxia-induced increases in reactive oxygen species activate NFATc3 increasing endothelin-1 vasoconstrictor reactivity.
Article in Vascular pharmacology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 36 citations in OpenAlex.
- L-Citrulline Supplementation Reduces Blood Pressure and Myocardial Infarct Size under Chronic Intermittent Hypoxia, a Major Feature of Sleep Apnea Syndrome.Antioxidants (Basel, Switzerland) · 2022Article
- Effects of intermittent hypoxia with thrombin in an in vitro model of human brain endothelial cells and their impact on PAR-1/PAR-3 cleavage.Scientific reports · 2022Article
- Oxygen therapy limiting peripheral oxygen saturation to 89-93% is associated with a better survival prognosis for critically ill COVID-19 patients at high altitudes.Respiratory physiology & neurobiology · 2022Observational
- O‑GlcNAcylation contributes to intermittent hypoxia‑associated vascular dysfunction via modulation of MAPKs but not CaMKII pathways.Molecular medicine reports · 2021Article
- Oxygen Biosensors and Control in 3D Physiomimetic Experimental Models.Antioxidants (Basel, Switzerland) · 2021Review
- High-altitude hypoxia induced reactive oxygen species generation, signaling, and mitigation approaches.International journal of biometeorology · 2021Review
- Simulated sleep apnea alters hydrogen sulfide regulation of blood flow and pressure.American journal of physiology. Heart and circulatory physiology · 2021Article
- Vascular Health Triad in Humans With Hypertension-Not the Usual Suspects.Frontiers in physiology · 2021Review
- Nonmuscle Myosin Light Chain Kinase: A Key Player in Intermittent Hypoxia-Induced Vascular Alterations.Journal of the American Heart Association · 2018Article
- The Role of Oxidative Stress in the Development of Systemic Sclerosis Related Vasculopathy.Frontiers in physiology · 2018Review
- NFATc3 and VIP in Idiopathic Pulmonary Fibrosis and Chronic Obstructive Pulmonary Disease.PloS one · 2017Article
- Targeting the ROS-HIF-1-endothelin axis as a therapeutic approach for the treatment of obstructive sleep apnea-related cardiovascular complications.Pharmacology & therapeutics · 2016Review
- Molecular and Cellular Mechanisms of Cardiovascular Disorders in Diabetes.Circulation research · 2016Review
- "TRP inflammation" relationship in cardiovascular system.Seminars in immunopathology · 2016Review
- Echocardiographic findings and plasma endothelin-1 levels in obese patients with and without obstructive sleep apnea.Sleep & breathing = Schlaf & Atmung · 2016Article
- Effect of hypoxia on TRPV1 and TRPV4 channels in rat pulmonary arterial smooth muscle cells.Pflugers Archiv : European journal of physiology · 2016Article
- Increased cerebrovascular sensitivity to endothelin-1 in a rat model of obstructive sleep apnea: a role for endothelin receptor B.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2015Article
- Regulation of signal transduction by reactive oxygen species in the cardiovascular system.Circulation research · 2015Review
- Retinal venous pressure in the non-affected eye of patients with retinal vein occlusions.Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie · 2014Article
- Endothelin-1-induced vasoconstriction does not require intracellular Ca²⁺ waves in arteries from rats exposed to intermittent hypoxia.American journal of physiology. Heart and circulatory physiology · 2014Article
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
Sleep apnea (SA), defined as intermittent respiratory arrest during sleep, is associated with increased incidence of hypertension, peripheral vascular disease, stroke, and sudden cardiac death. We have shown that intermittent hypoxia with CO2 supplementation (IH), a model for SA, increases blood pressure and circulating ET-1 levels, upregulates lung pre-pro ET-1 mRNA, increases vasoconstrictor reactivity to ET-1 in rat small mesenteric arteries (MA) and increases vascular reactive oxygen species (ROS). NFAT activity is increased in the aorta (AO) and MA of mice exposed to IH in an ET-1-dependent manner, and the genetic ablation of the isoform NFATc3 prevents IH-induced hypertension. We hypothesized that IH causes an increase in arterial ROS generation, which activates NFATc3 to increase vasoconstrictor reactivity to ET-1. In support of our hypothesis, we found that IH increases ROS in AO and MA. In vivo administration of the SOD mimetic tempol during IH exposure prevents IH-induced increases in NFAT activity in mouse MA and AO. We found that IH causes an NFATc3-dependent increase in vasoconstrictor reactivity to ET-1, accompanied by an increase in vessel wall [Ca²⁺]. Our results indicate that IH exposure causes an increase in arterial ROS to activate NFATc3, which then increases vasoconstrictor reactivity and Ca²⁺ response to ET-1. These studies highlight a novel regulatory pathway, and demonstrate the potential clinical relevance of NFAT inhibition to prevent hypertension in SA patients.
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